1. The Third International Consensus Definitions for Sepsis and
Septic Shock (Sepsis-3)
Singer M, et
al. JAMA. 2016;315(8):801-810.
Importance Definitions of sepsis and septic shock were
last revised in 2001. Considerable advances have since been made into the
pathobiology (changes in organ function, morphology, cell biology,
biochemistry, immunology, and circulation), management, and epidemiology of
sepsis, suggesting the need for reexamination.
Objective To evaluate and, as needed, update
definitions for sepsis and septic shock.
Process A task force (n = 19) with expertise in
sepsis pathobiology, clinical trials, and epidemiology was convened by the
Society of Critical Care Medicine and the European Society of Intensive Care
Medicine. Definitions and clinical criteria were generated through meetings,
Delphi processes, analysis of electronic health record databases, and voting,
followed by circulation to international professional societies, requesting
peer review and endorsement (by 31 societies listed in the Acknowledgment).
Key Findings
From Evidence Synthesis Limitations of
previous definitions included an excessive focus on inflammation, the
misleading model that sepsis follows a continuum through severe sepsis to
shock, and inadequate specificity and sensitivity of the systemic inflammatory
response syndrome (SIRS) criteria. Multiple definitions and terminologies are
currently in use for sepsis, septic shock, and organ dysfunction, leading to
discrepancies in reported incidence and observed mortality. The task force
concluded the term severe sepsis was redundant.
Recommendations Sepsis should be defined as life-threatening
organ dysfunction caused by a dysregulated host response to infection. For
clinical operationalization, organ dysfunction can be represented by an
increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA)
score of 2 points or more, which is associated with an in-hospital mortality
greater than 10%. Septic shock should be defined as a subset of sepsis in which
particularly profound circulatory, cellular, and metabolic abnormalities are
associated with a greater risk of mortality than with sepsis alone. Patients
with septic shock can be clinically identified by a vasopressor requirement to
maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate
level greater than 2 mmol/L (greater than 18 mg/dL) in the absence of
hypovolemia. This combination is associated with hospital mortality rates
greater than 40%. In out-of-hospital, emergency department, or general hospital
ward settings, adult patients with suspected infection can be rapidly
identified as being more likely to have poor outcomes typical of sepsis if they
have at least 2 of the following clinical criteria that together constitute a
new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min
or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less.
Conclusions
and Relevance These updated definitions
and clinical criteria should replace previous definitions, offer greater
consistency for epidemiologic studies and clinical trials, and facilitate
earlier recognition and more timely management of patients with sepsis or at
risk of developing sepsis.
Editorial:
New Sepsis Diagnostic Guidelines Shift Focus to Organ Dysfunction
Jacob, JA. JAMA
2016;315(8):739-740.
In March
2012, Rory Staunton, a 12-year-old boy in Queens, New York, cut his arm playing
basketball in school. The next day, his parents, worried about his fever and
leg pain, took him to see his pediatrician and then, the day after, to the
emergency department at NYU Langone Medical Center. He was discharged with a
diagnosis of an upset stomach and dehydration but died 3 days later from sepsis
(http://nyti.ms/1P8l3uR). His parents later founded the Rory Staunton
Foundation to increase public awareness of the condition (http://bit.ly/1ZEB798).
Rory’s story
illustrates the stealth and rapid progress of sepsis, which affects about 1
million people a year in the United States and kills about a quarter of those
affected (http://1.usa.gov/1Ig4SDq). New guidelines published in this issue of
JAMA, which are intended to increase the precision and speed of sepsis
diagnosis, shift the diagnostic focus from infection with systemic inflammation
to infection-triggered organ dysfunction, eliminate the distinction between
sepsis and severe sepsis, and refine the definition of septic shock (Singer M
et al. JAMA. 2016;315[8]:801-810).
A 19-member
joint task force of the Society of Critical Care Medicine (SCCM) and European
Society of Intensive Care Medicine (ESICM) developed the guidelines through
expert consensus and literature review, as well as by studying data from 1.3
million electronic health record (EHR) encounters of patients with suspected
infections who were treated at 12 hospitals within the University of Pittsburgh
Medical Center system from January 1, 2010, to December 31, 2012. Data were
also analyzed for an additional 706 399 patients from 4 EHR data sets within
and outside of the United States.
Based on the
assessment of the content validity, literature review, and expert deliberation,
the task force defined sepsis as a “life-threatening organ dysfunction caused
by a dysregulated host response to infection” (Singer M et al. JAMA.
2016;315[8]:801-810).
“[The task
force] felt very strongly that we needed to differentiate a straightforward
infection from one that can cause organ dysfunction or death,” said Mervyn
Singer, MD, the guidelines’ co-lead author and director of the Bloomsbury
Institute for Intensive Care Medicine at University College London. He
explained that this new emphasis on organ dysfunction, rather than infection,
stems from an evolving understanding of the pathophysiology of sepsis that
encompasses both inflammatory and anti-inflammatory responses and coagulation,
metabolic, and hormonal changes. Such changes cause a dysregulated response to
infection and can lead to organ dysfunction.
In addition,
the systemic inflammatory response syndrome (SIRS) criteria, which have been
used to diagnose sepsis for more than 20 years, can occur in normal disease
processes such as the common cold or even when a person vigorously exercises.
“[Sepsis] is
much more nuanced than previously appreciated,” explained Derek Angus, MD, MPH,
one of the guidelines’ coauthors and a professor and chair of the department of
critical care medicine at the University of Pittsburgh School of Medicine.
“Certain parts of the inflammatory response are overactive, and some are
underactive.”…
More
from Sepsis-3
A. Assessment of Clinical Criteria for
Sepsis
This cohort
study uses health system and research cohort data to compare the ability of
existing vs new clinical criteria for sepsis to identify intensive care unit
patients with suspected infection at higher mortality risk.
B. New Definition and Criteria for
Septic Shock
This article
describes the results of a meta-analysis of criteria used to identify adults
with septic shock and the processes by which a critical care task force used
the results to revise current septic shock definitions.
2. Effectiveness of Patient Choice in Nonoperative vs Surgical
Management of Pediatric Uncomplicated Acute Appendicitis
Minneci PC,
et al.
JAMA Surg.
Published online December 16, 2015.
Importance Current evidence suggests that nonoperative
management of uncomplicated appendicitis is safe, but overall effectiveness is
determined by combining medical outcomes with the patient’s and family’s
perspective, goals, and expectations.
Objective To determine the effectiveness of patient
choice in nonoperative vs surgical management of uncomplicated acute
appendicitis in children.
Design,
Setting, and Participants Prospective
patient choice cohort study in patients aged 7 to 17 years with acute
uncomplicated appendicitis presenting at a single pediatric tertiary acute care
hospital from October 1, 2012, through March 6, 2013. Participating patients
and families gave informed consent and chose between nonoperative management
and urgent appendectomy.
Interventions Urgent appendectomy or nonoperative
management entailing at least 24 hours of inpatient observation while receiving
intravenous antibiotics and, on demonstrating improvement of symptoms,
completion of 10 days of treatment with oral antibiotics.
Main Outcomes
and Measures The primary outcome was the
1-year success rate of nonoperative management. Successful nonoperative
management was defined as not undergoing an appendectomy. Secondary outcomes
included comparisons of the rates of complicated appendicitis, disability days,
and health care costs between nonoperative management and surgery.
Results A total of 102 patients were enrolled; 65
patients/families chose appendectomy (median age, 12 years; interquartile range
[IQR], 9-13 years; 45 male [69.2%]) and 37 patients/families chose nonoperative
management (median age, 11 years; IQR, 10-14 years; 24 male [64.9%]). Baseline
characteristics were similar between the groups. The success rate of
nonoperative management was 89.2% (95% CI, 74.6%-97.0%) at 30 days (33 of 37
children) and 75.7% (95% CI, 58.9%-88.2%) at 1 year (28 of 37 children). The
incidence of complicated appendicitis was 2.7% in the nonoperative group (1 of
37 children) and 12.3% in the surgery group (8 of 65 children) (P = .15). After
1 year, children managed nonoperatively compared with the surgery group had
fewer disability days (median [IQR], 8 [5-18] vs 21 [15-25] days, respectively;
P less than .001) and lower appendicitis-related health care costs (median
[IQR], $4219 [$2514-$7795] vs $5029 [$4596-$5482], respectively; P = .01).
Conclusions and
Relevance When chosen by the family,
nonoperative management is an effective treatment strategy for children with
uncomplicated acute appendicitis, incurring less morbidity and lower costs than
surgery.
3. In-Hospital Outcomes and Costs Among Patients Hospitalized
During a Return Visit to the ED
Sabbatini AK,
et al. JAMA. 2016 Feb 16;315(7):663-71.
IMPORTANCE:
Unscheduled short-term return visits to the emergency department (ED) are
increasingly monitored as a hospital performance measure and have been proposed
as a measure of the quality of emergency care.
OBJECTIVE: To
examine in-hospital clinical outcomes and resource use among patients who are
hospitalized during an unscheduled return visit to the ED.
DESIGN,
SETTING, AND PARTICIPANTS: Retrospective analysis of adult ED visits to acute
care hospitals in Florida and New York in 2013 using data from the Healthcare
Cost and Utilization Project. Patients with index ED visits were identified and
followed up for return visits to the ED within 7, 14, and 30 days.
EXPOSURES:
Hospital admission occurring during an initial visit to the ED vs during a
return visit to the ED.
MAIN OUTCOMES
AND MEASURES: In-hospital mortality, intensive care unit (ICU) admission, length
of stay, and inpatient costs.
RESULTS:
Among the 9,036,483 index ED visits to 424 hospitals in the study sample,
1,758,359 patients were admitted to the hospital during the index ED visit. Of
these patients, 149,214 (8.5%) had a return visit to the ED within 7 days of
the index ED visit, 228,370 (13.0%) within 14 days, and 349,335 (19.9%) within
30 days, and 76,151 (51.0%), 122,040 (53.4%), and 190,768 (54.6%),
respectively, were readmitted to the hospital. Among the 7,278,124 patients who
were discharged during the index ED visit, 598,404 (8.2%) had a return visit to
the ED within 7 days, 839,386 (11.5%) within 14 days, and 1,205,865 (16.6%)
within 30 days. Of these patients, 86,012 (14.4%) were admitted to the hospital
within 7 days, 121,587 (14.5%) within 14 days, and 173,279 (14.4%) within 30
days. The 86,012 patients discharged from the ED and admitted to the hospital
during a return ED visit within 7 days had significantly lower rates of
in-hospital mortality (1.85%) compared with the 1,609,145 patients who were
admitted during the index ED visit without a return ED visit (2.48%) (odds
ratio, 0.73 [95% CI, 0.69-0.78]), lower rates of ICU admission (23.3% vs 29.0%,
respectively; odds ratio, 0.73 [95% CI, 0.71-0.76]), lower mean costs ($10,169
vs $10,799; difference, $629 [95% CI, $479-$781]), and longer lengths of stay
(5.16 days vs 4.97 days; IRR, 1.04 [95% CI, 1.03-1.05]). Similar outcomes were
observed for patients returning to the ED within 14 and 30 days of the index ED
visit. In contrast, patients who returned to the ED after hospital discharge
and were readmitted had higher rates of in-hospital mortality and ICU
admission, longer lengths of stay, and higher costs during the repeat hospital
admission compared with those admitted to the hospital during the index ED
visit without a return ED visit.
CONCLUSIONS
AND RELEVANCE: Compared with adult patients who were hospitalized during the
index ED visit and did not have a return visit to the ED, patients who were
initially discharged during an ED visit and admitted during a return visit to
the ED had lower in-hospital mortality, ICU admission rates, and in-hospital
costs and longer lengths of stay. These findings suggest that hospital
admissions associated with return visits to the ED may not adequately capture
deficits in the quality of care delivered during an ED visit.
4. False negative interpretations of cranial CT in aneurysmal SAH.
Mark DG, et
al. Acad Emerg Med. 2016 Feb 26 [Epub ahead of print].
OBJECTIVES:
Prior studies examining the sensitivity of cranial computed tomography (CT) for
the detection of subarachnoid hemorrhage (SAH) have used the final radiology
report as the reference standard. However, optimal sensitivity may have been
underestimated due to misinterpretation of reportedly normal cranial CTs. This
study aims to estimate the incidence of missed CT evidence of SAH among a
cohort of patients with aneurysmal SAH (aSAH).
METHODS: We
performed a retrospective chart review of emergency department (ED) encounters
within an integrated health delivery system between January 2007 and June 2013
to identify patients diagnosed with aSAH. All initial non-contrast CTs from
aSAH cases diagnosed by lumbar puncture (LP) and angiography following a
reportedly normal non-contrast cranial CT (CT-negative aSAH) were then reviewed
in a blinded, independent fashion by two board-certified neuroradiologists to
assess for missed evidence of SAH. Reviewers rated the CT studies as having
either definite evidence of SAH, probable evidence of SAH, or no evidence of
SAH. Control patients who underwent a negative evaluation for aSAH based on
cranial CT and LP results were also included at random in the imaging review
cohort.
RESULTS: A
total of 452 cases of aSAH were identified; 18 (4%) were cases of CT-negative
aSAH. Of these, 7 (39%) underwent cranial CT within six hours of headache
onset, and 2 (11%) had their initial CTs formally interpreted by
board-certified neuroradiologists. Blinded independent CT review revealed
concordant agreement for either definite or probable evidence of SAH in 9 out
of 18 (50%) cases overall, and in 5 of the 7 (71%) CTs performed within six
hours of headache onset. Inter-rater agreement was 83% for definite SAH and 72%
for either probable or definite SAH.
CONCLUSIONS:
CT evidence of SAH was frequently present but unrecognized according to the
final radiology report in cases of presumed CT-negative aSAH. This finding may
help explain some of the discordance between prior studies examining the
sensitivity of cranial CT for SAH.
5. Effect of supplemental oxygen exposure on myocardial injury
in ST-elevation myocardial infarction
Nehme Z, et
al. Heart 2016 Mar;102(6):444-51.
OBJECTIVE: Supplemental
oxygen therapy may increase myocardial injury following ST-elevation myocardial
infarction (STEMI). In this study, we aimed to evaluate the effect of the dose
and duration of oxygen exposure on myocardial injury after STEMI.
METHODS: Descriptive
analysis of data from a multicentre, prospective, randomised, controlled trial
of 441 patients with STEMI randomised to supplemental oxygen therapy or room
air breathing. The primary endpoint was myocardial infarct size as assessed by
cardiac biomarkers, troponin (cTnI) and creatine kinase (CK). Oxygen therapy
was commenced by paramedics, and continued for up to 12 h postintervention in
hospital. Supplemental oxygen exposure was calculated as the area under the
dose×time curve for oxygen administration over the first 12 h, and then
assessed for its association with cTnI/CK release using multivariable linear
regression.
RESULTS: The
median supplemental oxygen exposure was 1746 L (IQR: 960-2858). After
adjustment for potential confounders, every 100 L increase in oxygen exposure
in the first 12 h was associated with a 1.4% (95% CI 0.6% to 2.2%, p less than 0.001)
and 1.2% (95% CI 0.7% to 1.8%, p less than 0.001) increase in the mean peak
cTnI and CK, respectively. Excluding patients who developed cardiogenic shock,
recurrent myocardial infarction or desaturations (SpO2 less than 94%) during
admission, every 100 L increase in oxygen exposure was associated with a 1.2%
(95% CI 0.2% to 2.1%, p=0.01) and 1.0% (95% CI 0.3% to 1.7%, p=0.003) increase
in the mean peak cTnI and CK, respectively. The median supplemental oxygen
exposure of 1746 L would result in a 21% (95% CI 3% to 37%) increase in infarct
size according to the cTnI profile.
CONCLUSIONS: Supplemental
oxygen exposure in the first 12 h after STEMI was associated with a clinically
significant increase in cTnI and CK release.
6. Myth busted: Fever not common symptom of teething
A study in
Pediatrics found the most common symptoms of teething in children include
irritated gums, irritability and drooling but not fever. Researchers analyzed
data from 16 studies and found tooth eruption could cause temperature to
increase but it could not be characterized as fever.
Massignan C,
et al. Signs and Symptoms of Primary Tooth Eruption: A Meta-analysis. Pediatrics
2016 Mar [Epub ahead of print]
CONTEXT:
Symptoms associated with the primary tooth eruption have been extensively
studied but it is still controversial.
OBJECTIVE: To
assess the occurrence of local and systemic signs and symptoms during primary
tooth eruption.
DATA SOURCES:
Latin American and Caribbean Health Sciences, PubMed, ProQuest, Scopus, and Web
of Science were searched. A partial gray literature search was taken by using
Google Scholar and the reference lists of the included studies were scanned.
STUDY
SELECTION: Observational studies assessing the association of eruption of
primary teeth with local and systemic signs and symptoms in children aged 0 to
36 months were included.
DATA
EXTRACTION: Two authors independently collected the information from the
selected articles. Information was crosschecked and confirmed for its accuracy.
RESULTS: A
total of 1179 articles were identified, and after a 2-phase selection, 16
studies were included. Overall prevalence of signs and symptoms occurring
during primary tooth eruption in children between 0 and 36 months was 70.5%
(total sample = 3506). Gingival irritation (86.81%), irritability (68.19%), and
drooling (55.72%) were the most frequent ones.
LIMITATIONS:
Different general symptoms were considered among studies. Some studies
presented lack of confounding factors, no clear definition of the diagnostics
methods, use of subjective measures and long intervals between examinations.
CONCLUSIONS:
There is evidence of the occurrence of signs and symptoms during primary tooth
eruption. For body temperature analyses, eruption could lead to a rise in
temperature, but it was not characterized as fever.
7. Risk of delayed ICH in anticoagulated patients after minor
head trauma: the role of repeat cranial CT.
Swap C, et
al. Perm J. 2016 Feb 15 [Epub ahead of print].
Context:
Patients receiving anticoagulant medications who experience minor head injury
are at increased risk of an intracerebral hemorrhage (ICH) developing, even
after an initial computed tomography (CT) scan of the brain yields normal
findings. Conflicting evidence exists regarding the frequency at which delayed
bleeding occurs.
Objective: To
identify the frequency of delayed traumatic ICH in patients receiving warfarin
or clopidogrel.
Design: We
performed a retrospective observational study of adult trauma encounters for
anticoagulated patients undergoing head CT at 1 of 13 Kaiser Permanente
Southern California Emergency Departments (EDs) between 2007 and 2011.
Encounters were identified using structured data from electronic health and
administrative records, and then records were individually reviewed for
validation of results.
Main Outcome
Measures: The primary outcome measure was ICH within 60 days of an ED visit
with a normal head CT result.
Results: Our
sample included 443 (260 clopidogrel and 183 warfarin) eligible ED encounters
with normal findings of initial head CT. Overall, 11 patients (2.5%, 95%
confidence interval [CI] = 1.4%-4.4%) had a delayed ICH, and events occurred at
similar rates between the clopidogrel group (6/260, 2.3%, CI 1.1%-5.0%) and
warfarin group (5/183, 2.7%, CI 1.2%-6.2%).
Conclusion:
Trauma patients in the ED who are receiving warfarin or clopidogrel have
approximately a 2.5% risk of delayed ICH after an initial normal finding on a
head CT.
Full-text: http://www.thepermanentejournal.org/issues/2016/spring/6042-intracerebral-hemorrhage.html
8. Brief Lit Reviews from Ann Emerg Med
A. Are Antibiotics Effective in the
Treatment of Acute Maxillary Sinusitis?
Moderate
evidence suggests that antibiotics provide a small clinical benefit for the
treatment of acute maxillary sinusitis, defined as a maxillary sinus infection
with an onset of fewer than 4 weeks. However, approximately 80% of patients
improve within 2 weeks without any antibiotic treatment.
B. Does Intubation Improve Outcomes
Over Supraglottic Airways in Adult Out-of-Hospital Cardiac Arrest?
In
observational studies, intubation is associated with better outcomes than
supraglottic airway devices in out-of-hospital cardiac arrest; however, the
results of ongoing prospective trials are needed to confirm these findings.
C. Is Single-Dose Etomidate Induction
Safe in Emergency Intubation of Critically Ill Patients?
Single-use
etomidate in intubation for critically ill patients may result in transient
adrenal and other organ dysfunction, but with no effect on mortality.
9. Evidence-Based Guideline: Treatment of Convulsive Status
Epilepticus in Children and Adults: Report of the Guideline Committee of the
American Epilepsy Society
Glauser T, et
al. Epilepsy Currents 2016;
The following
organizations have endorsed this guideline: Epilepsy Foundation, Child
Neurology Society, American College of Emergency Physicians, Association of
Child Neurology Nurses, American Association of Neuroscience Nurses.
The analysis
addressed five questions involving adults/children with seizures lasting more
than 5 minutes:
Q1. Which
anticonvulsants are efficacious as initial and subsequent therapy?
Q2. What
adverse events are associated with anticonvulsant administration?
Q3. Which is
the most effective benzodiazepine?
Q4. Is IV
fosphenytoin more effective than IV phenytoin?
Q5. When does
anticonvulsant efficacy drop significantly (i.e., after how many different
anticonvulsants does status epilepticus become refractory)?
CONTEXT: The
optimal pharmacologic treatment for early convulsive status epilepticus is
unclear.
OBJECTIVE: To
analyze efficacy, tolerability and safety data for anticonvulsant treatment of
children and adults with convulsive status epilepticus and use this analysis to
develop an evidence-based treatment algorithm.
DATA SOURCES:
Structured literature review using MEDLINE, Embase, Current Contents, and
Cochrane library supplemented with article reference lists.
STUDY
SELECTION: Randomized controlled trials of anticonvulsant treatment for
seizures lasting longer than 5 minutes.
DATA
EXTRACTION: Individual studies were rated using predefined criteria and these
results were used to form recommendations, conclusions, and an evidence-based
treatment algorithm.
RESULTS: A
total of 38 randomized controlled trials were identified, rated and contributed
to the assessment. Only four trials were considered to have class I evidence of
efficacy. Two studies were rated as class II and the remaining 32 were judged
to have class III evidence. In adults with convulsive status epilepticus,
intramuscular midazolam, intravenous lorazepam, intravenous diazepam and
intravenous phenobarbital are established as efficacious as initial therapy
(Level A). Intramuscular midazolam has superior effectiveness compared to
intravenous lorazepam in adults with convulsive status epilepticus without
established intravenous access (Level A). In children, intravenous lorazepam
and intravenous diazepam are established as efficacious at stopping seizures
lasting at least 5 minutes (Level A) while rectal diazepam, intramuscular
midazolam, intranasal midazolam, and buccal midazolam are probably effective
(Level B). No significant difference in effectiveness has been demonstrated between
intravenous lorazepam and intravenous diazepam in adults or children with
convulsive status epilepticus (Level A).
Respiratory
and cardiac symptoms are the most commonly encountered treatment-emergent
adverse events associated with intravenous anticonvulsant drug administration
in adults with convulsive status epilepticus (Level A). The rate of respiratory
depression in patients with convulsive status epilepticus treated with
benzodiazepines is lower than in patients with convulsive status epilepticus
treated with placebo indicating that respiratory problems are an important
consequence of untreated convulsive status epilepticus (Level A). When both are
available, fosphenytoin is preferred over phenytoin based on tolerability but
phenytoin is an acceptable alternative (Level A). In adults, compared to the
first therapy, the second therapy is less effective while the third therapy is
substantially less effective (Level A). In children, the second therapy appears
less effective and there are no data about third therapy efficacy (Level C).
The evidence was synthesized into a treatment algorithm.
CONCLUSIONS:
Despite the paucity of well-designed randomized controlled trials, practical
conclusions and an integrated treatment algorithm for the treatment of
convulsive status epilepticus across the age spectrum (infants through adults)
can be constructed. Multicenter, multinational efforts are needed to design,
conduct and analyze additional randomized controlled trials that can answer the
many outstanding clinically relevant questions identified in this guideline.
10. Images in Clinical Practice
Scalp
Necrosis Associated with Giant-Cell Arteritis
Worm-induced
biliary obstruction. http://www.thepermanentejournal.org/issues/2016/spring/6030-biliary-obstruction.html
Geographic
Tongue
Central
Pontine Myelinolysis
Adult Female
With Dyspnea
Elderly Man
With Acute Respiratory Distress
Young Man
With Lump in His Neck
Discussion
of Neck Lump: The Lowdown on Ventriculoperitoneal Shunts
Adult Female
With Chest Pain
Child With
Chest Pain Diagnosed With Pneumonia
Newborn
Infant With Respiratory Distress
Man With
Finger Injury
Ocular
Rosacea
Eggshell
Calcifications of the Bladder
Shot in the
Heart
A Rare Cause of Headache
Tension Hydrothorax Related to
Disseminated Endometriosis
11. Apneic oxygenation is associated with a reduction in the
incidence of hypoxemia during the RSI of patients with ICH in the ED.
Sakles JC, et
al. Intern Emerg Med. 2016 Feb 4. [Epub ahead of print]
Critically
ill patients undergoing emergent intubation are at risk of oxygen desaturation
during the management of their airway. Patients with intracranial hemorrhage
(ICH) are particularly susceptible to the detrimental effects of hypoxemia.
Apneic oxygenation (AP OX) may be able to reduce the occurrence of oxygen
desaturation during the emergent intubation of these patients. We sought to
assess the effect AP OX on oxygen desaturation during the rapid sequence
intubation (RSI) of patients with ICH in the emergency department (ED).
We
prospectively collected data on all patients intubated in an urban academic ED
over the 2-year period from July 1, 2013 to June 30, 2015. Following each
intubation, the operator completed a standardized continuous quality improvement
(CQI) data form, which included information on patient, operator and intubation
characteristics. Operators recorded data on the use of AP OX, the oxygen flow
rate used for AP OX, and the starting and lowest saturations during intubation.
Adult patients with ICH who underwent RSI by emergency medicine (EM) residents
were included in the analyses. The primary outcome variable was any oxygen
saturation less than 90 % during the intubation. We performed a backward
stepwise multivariate logistic regression analysis to identify variables
associated with oxygen desaturation. The primary independent variable of
interest was the use of AP OX during the intubation.
Inclusion
criteria for the study was met by 127 patients. AP OX was used in 72 patients
(AP OX group) and was not used in 55 patients (NO AP OX group). The incidence
of desaturation was 5/72 (7 %) in the AP OX group and was 16/55 (29 %) in the
NO AP OX group. In the multivariate logistic regression analysis the use of AP
OX was associated with a reduced odds of desaturation (aOR 0.13; 95 % CI
0.03-0.53). Patients with ICH who received AP OX during RSI in the ED were
seven times less likely to have an oxygen saturation of less than 90 % during
the intubation compared to patients who did not receive AP OX.
AP OX is a
simple intervention that may minimize the risk of oxygen desaturation during
the RSI of patients with ICH.
12. ST depression in lead aVL differentiates inferior
ST-elevation MI from pericarditis.
Bischof JE,
et al. Am J Emerg Med. 2016 Feb;34(2):149-54.
BACKGROUND:
ST-segment elevation (STE) due to inferior STE myocardial infarction (STEMI)
may be misdiagnosed as pericarditis. Conversely, this less life-threatening
etiology of ST elevation may be confused for inferior STEMI. We sought to
determine if the presence of any ST-segment depression in lead aVL would
differentiate inferior STEMI from pericarditis.
METHODS:
Retrospective study of 3 populations. Cohort 1 included patients coded as
inferior STEMI, cohort 2 included patients with a discharge diagnosis of
pericarditis who presented with chest pain and at least 0.5 mm of ST elevation
in at least 1 inferior lead. We analyzed the presenting electrocardiogram in
both populations, with careful assessment of leads II, III, aVF, and aVL. In
addition, we retrospectively studied a third cohort of patients with subtle
inferior STEMI (less than 1-mm STE with occluded artery on catheterization) and
assessed the sensitivity of ST depression in lead aVL for this group.
RESULTS: Of
154 inferior STEMI patients, 154 had some amount of ST depression in lead aVL
(100%; confidence interval, 98%-100%). Of the 49 electrocardiograms in the
pericarditis group, all 49 had some inferior STE but none had any ST-segment
depression in lead aVL (specificity, 100%; confidence interval, 91%-100%). In
the third cohort, there were 272 inferior MIs with coronary occlusion, of which
54 were "subtle." Of these, 49 had some ST depression in lead aVL.
CONCLUSION:
When there is inferior ST-segment elevation, the presence of any ST depression
in lead aVL is highly sensitive for coronary occlusion in inferior myocardial
infarction and very specific for differentiating inferior myocardial infarction
from pericarditis.
13. Ask Your Doctor if This Ad Is Right for You: How advertising
promotes expensive drugs and treatments you may not need.
By Elisabeth
Rosenthal. New York Times. FEB. 27, 2016
A LITTLE more
than a decade ago, most health care advertising was confined to mass-market
drugs, and hospitals and doctors generally considered the practice tacky or
ethically dubious. More often than not, the ads appeared in unassuming places
like cheaper women’s magazines or the New York subway — for decades New Yorkers
sat beneath ubiquitous rainbow posters for Dr. Jonathan Zizmor that promised to
conquer blemishes: 212-594-SKIN!
But today,
health care advertising is skyrocketing and likely to turn up in business-class
lounges in airport terminals or the Jitney to the Hamptons. It occupies the
center spreads and back covers of elite magazines alongside plugs for luxury
watches, jewelry and resorts. On television it has found its way into
prime-time slots: presidential debates, primary campaign coverage and even the
Super Bowl.
The ads are
targeting a far more rarefied market than in the past: patients with good
insurance or those who can pay out of pocket for the priciest drugs. Hospitals
and clinics have also jumped into the fray: What hospital or clinic these days
doesn’t trumpet its services to its customer base (people formerly known as
patients)?
Drug
companies, which once focused mainly on promoting products like painkillers
that might be prescribed to millions, now advertise costly niche medicines that
might be prescribed to thousands. Ads from the medical profession don’t focus
on small-bore items like Dr. Z’s blemish remedies, but big-ticket treatments
like joint replacements and cancer care.
The health
care industry spent $14 billion on advertising in 2014, according to Kantar
Media, a jump of nearly 20 percent since 2011. That includes over-the-counter
medications, but not sponsorships (the Super Bowl had two health care systems
as partners). While magazine advertising has dropped off somewhat with the
withering of the publishing industry, television advertising has risen 55
percent for hospitals and 30 percent for prescription drugs in that period.
“The stage is
beyond crowded, and everyone wants to be seen as shaping their brand and being
the patients’ partner of choice,” said Lisa Kerins, a managing director at the
Nielsen Company, who said that ad spending for hospitals had increased by 33
percent since the beginning of 2012.
Last weekend’s
episode of “60 Minutes,” for example, included advertising for four expensive
drugs and two hospitals, Memorial Sloan Kettering Cancer Center and NYU Langone
Medical Center. Meanwhile, The New York Times Magazine on the same weekend
featured glossy full-page promotions for hospitals in New York, Denver and
Boston, competing for space with ads for spas and hotels…
The remainder
of the essay: http://www.nytimes.com/2016/02/28/sunday-review/ask-your-doctor-if-this-ad-is-right-for-you.html
14. Oral Prednisolone in the Treatment of Acute Gout: A
Pragmatic, Multicenter, Double-Blind, Randomized Trial.
Rainer TH, et
al. Ann Intern Med. 2016 Feb 23 [Epub ahead of print]
Background:
Two recent double-blind randomized, controlled trials (RCTs) showed that oral
steroids and nonsteroidal anti-inflammatory drugs have similar analgesic
effectiveness for management of gout, but the trials had small sample sizes and
other methodological limitations.
Objective: To
compare the effectiveness and safety of oral prednisolone versus oral
indomethacin in patients presenting to emergency departments (EDs) with acute
gout.
Design:
Multicenter, double-blind, randomized equivalence trial. Patients were randomly
assigned (1:1 ratio) to receive either indomethacin or prednisolone. (ISRCTN
registry number: ISRCTN45724113).
Setting: Four
EDs in Hong Kong.
Participants:
416 patients aged 18 years or older.
Measurements:
Analgesic effectiveness was defined as changes in pain (at rest or with
activity) greater than 13 mm on a 100-mm visual analogue scale. Outcomes were
measured during the first 2 hours in the ED and from days 1 to 14.
Results:
376 patients completed the study. Equivalent and clinically significant
within-group reductions in mean pain score were observed with indomethacin and
prednisolone in the ED (approximately 10 mm [rest] and 20 mm [activity]) and
from days 1 to 14 (approximately 25 mm [rest] and 45 mm [activity]). No major
adverse events occurred during the study. During the ED phase, patients in the
indomethacin group had more minor adverse events than those in the prednisolone
group (19% vs. 6%; P less than 0.001). During days 1 to 14, 37% of patients in
each group had minor adverse events.
Limitation:
Diagnosis of gout was usually based on clinical criteria rather than
examination of joint fluid.
Conclusion:
Oral prednisolone and indomethacin had similar analgesic effectiveness among
patients with acute gout. Prednisolone is an effective and safe first-line
option for treatment of acute gout.
15. Point-of-Care Multi-Organ Ultrasound Improves Diagnostic
Accuracy in Adults Presenting to the ED with Acute Dyspnea
Mantuani D,
et al. West J Emerg Med. 2016;17(1):46-53.
Introduction:
Determining the etiology of acute dyspnea in emregency department (ED) patients
is often difficult. Point-of-care ultrasound (POCUS) holds promise for
improving immediate diagnostic accuracy (after history and physical), thus
improving use of focused therapies. We evaluate the impact of a three-part
POCUS exam, or “triple scan” (TS) – composed of abbreviated echocardiography,
lung ultrasound and inferior vena cava (IVC) collapsibility assessment – on the
treating physician’s immediate diagnostic impression.
Methods: A
convenience sample of adults presenting to our urban academic ED with acute
dyspnea (Emergency Severity Index 1, 2) were prospectively enrolled when
investigator sonographers were available. The method for performing components
of the TS has been previously described in detail. Treating physicians rated
the most likely diagnosis after history and physical but before other studies
(except electrocardiogram) returned. An investigator then performed TS and disclosed
the results, after which most likely diagnosis was reassessed. Final diagnosis
(criterion standard) was based on medical record review by expert emergency
medicine faculty blinded to TS result. We compared accuracy of pre-TS and
post-TS impression (primary outcome) with McNemar’s test. Test characteristics
for treating physician impression were also calculated by dichotomizing acute
decompensated heart failure (ADHF), chronic obstructive pulmonary disease
(COPD) and pneumonia as present or absent.
Results: 57
patients were enrolled with the leading final diagnoses being ADHF (26%),
COPD/asthma (30%), and pneumonia (28%). Overall accuracy of the treating
physician’s impression increased from 53% before TS to 77% after TS (p=0.003).
The post-TS impression was 100% sensitive and 84% specific for ADHF.
Conclusion:
In this small study, POCUS evaluation of the heart, lungs and IVC improved the
treating physician’s immediate overall diagnostic accuracy for ADHF,
COPD/asthma and pneumonia and was particularly useful to immediately exclude
ADHF as the cause of acute dyspnea.
16. ED Prescription Opioids May Contribute to Risk for Addiction
A. ED Prescription Opioids as an
Initial Exposure Preceding Addiction.
Butler MM, et
al. Ann Emerg Med. 2016 Feb 10. [Epub ahead of print]
STUDY
OBJECTIVE: Opioid abuse and overdose constitute an ongoing health emergency.
Many presume opioids have little potential for iatrogenic addiction when used
as directed, particularly in short courses, as is typical of the emergency
department (ED) setting. We preliminarily explore the possibility that initial
exposure to opioids by EDs could be related to subsequent opioid misuse.
METHODS: This
cross-sectional study surveyed a convenience sample of patients reporting
heroin or nonmedical opioid use at an urban, academic ED. We estimated the
proportion whose initial exposure to opioids was a legitimate medical
prescription and the proportion of those prescriptions that came from an ED.
Secondary measurements included the proportion of patients receiving nonopioid
substances before initial opioid exposure, the source of opioids between
initial exposure and onset of regular nonmedical use, and time from initial
prescription to opioid use disorder.
RESULTS: Of
59 subjects, 35 (59%; 95% confidence interval [CI] 47% to 71%) reported they
were first exposed to opioids by a legitimate medical prescription, and for 10
of 35 (29%; 95% CI 16% to 45%), the prescription came from an ED. Most
medically exposed subjects (28/35; 80%; 95% CI 65% to 91%) reported nonopioid
substance use or treatment for nonopioid substance use disorders preceding the
initial opioid exposure. Emergency providers were a source of opioids between
exposure and onset of regular nonmedical use in 11 of 35 cases (31%; 95% CI 18%
to 48%). Thirty-one of the 35 medically exposed subjects reported the time of
onset of nonmedical use; median time from exposure to onset of nonmedical use was
6 months for use to get high (N=25; interquartile range [IQR] 2 to 36), 12
months for regular use to get high (N=24; IQR 2 to 36), 18 months for use to
avoid withdrawal (N=26; IQR 2 to 38), and 24 months for regular use to avoid
withdrawal (N=27; IQR 2 to 48). Eleven subjects (36%; 95% CI 21% to 53%) began
nonmedical use within 2 months, and 9 of 11 (82%; 95% CI 53% to 96%) reported
nonopioid substance use or treatment for alcohol abuse before initial opioid
exposure.
CONCLUSION: Although
short-term opioid administration by emergency providers is unlikely to cause
addiction by itself, ED opioid prescriptions may contribute to the development
of addiction in some patients. There is an urgent need for further research to
estimate long-term risks of short-course opioid therapy so that the risk of
iatrogenic addiction can be appropriately balanced with the benefit of
analgesia.
B. Extent and Impact of Opioid
Prescribing for Acute Occupational Low Back Pain in the ED
Lee SS, et
al. J Emerg Med. 2016 Mar;50(3):376-384.e2
BACKGROUND:
Initial management of acute occupational low back pain (AOLBP) commonly occurs
in the emergency department (ED), where opioid prescribing can vary from the
clinical guidelines that recommend limited use.
OBJECTIVE:
The objective of this study was to explore how opioids are prescribed in the ED
and the impact on work disability and other outcomes in AOLBP.
METHODS: A
retrospective cohort study was conducted. All acute compensable lost-time LBP
cases seen initially in the ED with a date of injury from January 1, 2009 to
December 31, 2011 were identified within a nationally representative Workers'
Compensation dataset. Multivariate models estimated the effect of early opioids
(received within 2 days of ED visit) on disability duration, long-term opioid
use, total medical costs, and subsequent surgeries.
RESULTS: Of
the cohort (N = 2887), 12% received early opioids; controlling for severity,
this was significantly associated with long-term opioid use (adjusted risk
ratio = 1.29; 95% confidence interval 1.05-1.58) and increased total medical
costs for those in the highest opioid dosage quartile, but not associated with
disability duration or subsequent low back surgery.
CONCLUSIONS:
Early opioid prescribing in the ED for uncomplicated AOLBP increased long-term
opioid use and medical costs, and should be discouraged, as opioid use for low
back pain has been associated with a variety of adverse outcomes. However, ED
providers may be becoming more compliant with current LBP treatment guidelines.
17. Antibiotic Therapy for Adults Hospitalized With
Community-Acquired Pneumonia: A Systematic Review
Lee JS, et
al. JAMA. 2016;315(6):593-602
Importance Antibiotic therapy is the cornerstone of
medical management for community-acquired pneumonia.
Objective To assess the associations between 3 key
aspects of antibiotic therapy (optimal time to antibiotic initiation, initial
antibiotic selection, and criteria for the transition from intravenous to oral
therapy) and short-term mortality in adults hospitalized with
community-acquired pneumonia.
Evidence
Review Bibliographic databases of
MEDLINE, EMBASE, and the Cochrane Collaboration were searched for studies of
adults hospitalized with radiographically confirmed community-acquired
pneumonia published from January 1, 1995, until November 5, 2015.
Findings Twenty studies (17 observational and 3
randomized trials) met eligibility criteria. Among 8 observational studies
identified, the 4 largest (study populations of 2878 to 1 170 022) found that
antibiotic initiation within 4 to 8 hours of hospital arrival was associated with
relative reductions of 5% to 43% in mortality; the 4 smallest studies (study
populations of 451 to 2076) found no associations between the timing of
antibiotic initiation and mortality. One cluster randomized trial (n = 1737)
demonstrated noninferiority of β-lactam monotherapy (n = 506) vs β-lactam plus
macrolide combination therapy (n = 566), with an absolute adjusted difference
of 2.5% (90% CI, −0.6% to 5.2%) in 90-day mortality favoring β-lactam
monotherapy. A second randomized trial (n = 580) failed to demonstrate
noninferiority of β-lactam monotherapy vs β-lactam plus macrolide combination
therapy, with an absolute difference of 7.6% (1-sided 90% CI upper limit,
13.0%) in attainment of clinical stability on hospital day 7 favoring β-lactam
plus macrolide combination therapy. Six of 8 observational studies (study
populations of 1188 to 24 780) found that β-lactam plus macrolide combination
therapy was associated with relative reductions of 26% to 68% in short-term
mortality and all 3 observational studies (study populations of 2068 to 24 780)
reported that fluoroquinolone monotherapy was associated with relative
reductions of 30% to 43% in mortality compared with β-lactam monotherapy. One
randomized trial (n = 302) reported significantly reduced hospital length of
stay (absolute difference, 1.9 days; 95% CI, 0.6 to 3.2 days), but no
differences in treatment failure when objective clinical criteria were used to
decide when to transition patients from intravenous to oral therapy.
Conclusions
and Relevance In adults hospitalized
with community-acquired pneumonia, antibiotic therapy consisting of β-lactam
plus macrolide combination therapy or fluoroquinolone monotherapy initiated
within 4 to 8 hours of hospital arrival was associated with lower adjusted short-term
mortality, supported predominantly by low-quality observational studies. One
randomized trial supports the use of objective clinical criteria to guide the
transition from intravenous to oral antibiotic therapy.
18. Adjunctive Dexamethasone worsened outcomes in HIV-Associated
Cryptococcal Meningitis
Beardsley J,
et al. N Engl J Med. 2016 Feb 11;374(6):542-54.
BACKGROUND:
Cryptococcal meningitis associated with human immunodeficiency virus (HIV)
infection causes more than 600,000 deaths each year worldwide. Treatment has
changed little in 20 years, and there are no imminent new anticryptococcal
agents. The use of adjuvant glucocorticoids reduces mortality among patients
with other forms of meningitis in some populations, but their use is untested
in patients with cryptococcal meningitis.
METHODS: In
this double-blind, randomized, placebo-controlled trial, we recruited adult
patients with HIV-associated cryptococcal meningitis in Vietnam, Thailand,
Indonesia, Laos, Uganda, and Malawi. All the patients received either
dexamethasone or placebo for 6 weeks, along with combination antifungal therapy
with amphotericin B and fluconazole.
RESULTS: The
trial was stopped for safety reasons after the enrollment of 451 patients.
Mortality was 47% in the dexamethasone group and 41% in the placebo group by 10
weeks (hazard ratio in the dexamethasone group, 1.11; 95% confidence interval
[CI], 0.84 to 1.47; P=0.45) and 57% and 49%, respectively, by 6 months (hazard
ratio, 1.18; 95% CI, 0.91 to 1.53; P=0.20). The percentage of patients with
disability at 10 weeks was higher in the dexamethasone group than in the
placebo group, with 13% versus 25% having a prespecified good outcome (odds
ratio, 0.42; 95% CI, 0.25 to 0.69; P less than 0.001). Clinical adverse events
were more common in the dexamethasone group than in the placebo group (667 vs.
494 events, P=0.01), with more patients in the dexamethasone group having grade
3 or 4 infection (48 vs. 25 patients, P=0.003), renal events (22 vs. 7,
P=0.004), and cardiac events (8 vs. 0, P=0.004). Fungal clearance in
cerebrospinal fluid was slower in the dexamethasone group. Results were
consistent across Asian and African sites.
CONCLUSIONS:
Dexamethasone did not reduce mortality among patients with HIV-associated
cryptococcal meningitis and was associated with more adverse events and
disability than was placebo.
19. Assessment of Common Preoxygenation Strategies Outside of
the OR Environment.
Groombridge C,
et al. Acad Emerg Med. 2016 Jan 4 [Epub
ahead of print]
OBJECTIVES: Preoxygenation
prior to intubation aims to increase the duration of safe apnea by causing
denitrogenation of the functional residual capacity, replacing this volume with
a reservoir of oxygen. In the operating room (OR) the criterion-standard for
preoxygenation is an anesthetic circuit and well-fitting face mask, which
provide a high fractional inspired oxygen concentration (FiO2 ). Outside of the
OR, various strategies exist to provide preoxygenation. The objective was to
evaluate the effectiveness of commonly used preoxygenation strategies outside
of the OR environment.
METHODS: This
was a prospective randomized unblinded study of 30 healthy staff volunteers
from a major trauma center emergency department (ED) in Sydney, Australia. The
main outcome measure is fractional expired oxygen concentration (FeO2 )
measured after a 3 minute period of tidal volume breathing with seven different
preoxygenation strategies.
RESULTS: The
mean FeO2 achieved with the anesthetic circuit was 81.0% (95% CI = 78.3% to
83.6%), bag-valve-mask (BVM) 80.1% (95% CI = 76.5% to 83.6%), BVM with nasal
cannulae (NC) 74.8% (95% CI = 72.0% to 77.6%), BVM with positive end expiratory
pressure valve (PEEP) 78.9% (95% CI = 75.4% to 82.3%), BVM + NC + PEEP 75.5%
(95% CI = 72.2% to 78.9%), non-rebreather mask (NRM) 51.6% (95% CI = 48.8% to
54.4%), and NRM + NC 57.1% (95% CI = 52.9% to 61.2%). Preoxygenation efficacy
with BVM strategies was significantly greater than NRM strategies (p less than
0.01), and non-inferior to the anesthetic circuit.
CONCLUSIONS:
In healthy volunteers, the effectiveness of BVM preoxygenation was comparable
to the anesthetic circuit (criterion standard), and superior to preoxygenation
with NRM. The addition of nasal cannulae oxygen, PEEP, or both, did not improve
the efficacy of the BVM device.
20. Frequency of Fractures Identified on Post-Reduction
Radiographs after Shoulder Dislocation
Gottlieb M,
et al. West J Emerg Med 2016;17(1):35-8.
Introduction:
Most emergency physicians routinely obtain shoulder radiographs before and
after shoulder dislocations. However, currently there is limited literature
demonstrating how frequently new fractures are identified on post-reduction
radiographs. The primary objective of this study was to determine the frequency
of new, clinically significant fractures identified on post-reduction
radiographs with a secondary outcome assessing total new fractures identified.
Methods: We
conducted a retrospective chart review using appropriate International
Classification of Diseases, 9th Revision (ICD-9) codes to identify all
potential shoulder dislocations that were reduced in a single, urban, academic
emergency department (ED) over a five-year period. We excluded cases that
required operative reduction, had associated proximal humeral head or shaft
fractures, or were missing one or more shoulder radiograph reports. All charts
were abstracted separately by two study investigators with disagreements settled
by consensus among three investigators. Images from indeterminate cases were
reviewed by a radiology attending physician with musculoskeletal expertise. The
primary outcome was the percentage of new, clinically significant fractures
defined as those altering acute ED management. Secondary outcomes included
percentage of new fractures of any type.
Results: We
identified 185 total patients meeting our study criteria. There were no new,
clinically significant fractures on post-reduction radiographs. There were 13
(7.0%; 95% CI [3.3%-10.7%]) total new fractures identified, all of which were
without clinical significance for acute ED management.
Conclusion:
Post-reduction radiographs do not appear to identify any new, clinically
significant fractures. Practitioners should re-consider the use of routine
post-reduction radiographs in the ED setting for shoulder dislocations.
21. Prospective comparison of ultrasound and CXR for
confirmation of central vascular catheter placement
Weekes AJ, et
al. Emerg Med J 2016;33:176-180
Objective To
prospectively compare ultrasound (US) versus CXR for confirmation of central
vascular catheter (CVC) placement. Secondary objective was to determine the
incidence of pneumothorax (PTX) and compare US with CXR completion times.
Methods
Investigators performed the US saline flush echo test, and evaluated each
anterior hemithorax for pleural sliding with US after subclavian or internal
jugular CVC placement.
Measurements
and main results 151 total (135 in the emergency department, 16 in the
intensive care unit) patients after CVC placement, mean age 62.1±15.6 years and
83 (55%) female patients. The rapid atrial swirl sign ( RASS) was ultrasound
finding of an immediate appearance of turbulence entering the right atrium via
superior vena cava after a rapid saline flush of the distal CVC port. RASS was
considered ‘negative’ for CVC malposition. US identified all correct CVC
placements. Four suboptimal CVC tip placements were detected by CXR. US
identified three of these misplacements (McNemar exact p value above 0.99).
There were no cases of PTX or abnormal pleural sliding by either CXR or US.
Median times for US and CXR completion were 1.1 (IQR 0.7) minutes and 20 (IQR:
30) minutes, respectively, median difference 23.8 (95% CI 19.6 to 29.3)
minutes, p less than 0.0001.
Conclusions
PTX and CVC tip malposition were rare after US-guided CVC placement. There was
no significant difference between saline flush echo and CXR for the
identification of catheter tip malposition. Benefits of US assessment for
complications include reduced radiation exposure and time delays associated
with CXR.
22. Studies of the New Oral Anticoagulants
A. An Observational Study of the
Factor Xa Inhibitors Rivaroxaban and Apixaban as Reported to Eight Poison
Centers.
Data from 8
poison control centers show no bleeding in cases of single ingestions of
apixaban or rivaroxaban.
Spiller HA,
et al. Ann Emerg Med. 2016 Feb;67(2):189-95.
STUDY
OBJECTIVE: Rivaroxaban and apixaban are part of a new group of oral
anticoagulants targeting factor Xa and approved by the Food and Drug
Administration in 2011 and 2012. These oral anticoagulants are administered at
fixed daily doses, without the need for laboratory-guided adjustments. There
are limited data available on supratherapeutic doses or overdose of the oral Xa
inhibitors. This study characterizes the clinical effect in patients exposed to
rivaroxaban and apixaban.
METHODS: A
retrospective study collected data from 8 regional poison centers covering 9
states. Cases were initially identified by a search of the poison centers'
databases for case mentions involving a human exposure to Xarelto, rivaroxaban,
Eliquis, or apixaban. Inclusion criteria included single-substance exposure.
Exclusion criteria were animal exposure, polysubstance exposure, or information
call. Data for the study were collected by individual chart review, including
case narratives, and compiled into a single data set.
RESULTS:
There were 223 patients: 124 (56%) were female patients, mean age was 60 years,
and 20 were children younger than 12 years (9%). One hundred ninety-eight
patients ingested rivaroxaban (89%) and 25 ingested apixaban (11%). Dose was
reported in 182 rivaroxaban patients, with a mean dose of 64.5 mg (range 15 to
1,200 mg), and in 21 apixaban patients, with a mean dose of 9.6 mg (range 2.5
to 20 mg). For rivaroxaban, prothrombin time was measured in 49 patients (25%)
and elevated in 7; partial thromboplastin time, measured in 49 (25%) and
elevated in 5; and international normalized ratio, measured in 61 (31%) and
elevated in 13. For apixaban, prothrombin time was measured in 6 patients (24%)
and elevated in none; partial thromboplastin time, measure in 6 (24%) and
elevated in none; and international normalized ratio, measured in 5 patients (20%)
and elevated in none. Bleeding was reported in 15 patients (7%): 11 rivaroxaban
and 4 apixaban. The site of bleeding was gastrointestinal (8), oral (2), nose
(1), bruising (1), urine (1), and subdural (1). The subdural bleeding occurred
after fall and head injury. All cases with bleeding involved long-term
ingestions. Coagulation test results were normal in most patients with
bleeding: prothrombin time 5 of 6 (83%), partial thromboplastin time 5 of 6
(83%), and international normalized ratio 5 of 9 (55%). Blood products were
used in 7 rivaroxaban patients (1 suicide) and 3 apixaban patients. No bleeding
or altered coagulation test results occurred in children, which all involved a
one-time ingestion. All 12 suicide attempts involved rivaroxaban: altered coagulation
test results occurred for 5 patients (42%), no bleeding occurred in any suicide
attempt patient, 1 patient was treated with fresh frozen plasma (international
normalized ratio 12.47), and dose by patient history did not predict risk of
altered coagulation or bleeding. Two rivaroxaban patients experienced elevation
of hepatic transaminase levels greater than 1,000 U/L.
CONCLUSION:
Bleeding after Xa inhibitor ingestion as a single agent is uncommon.
Prothrombin time, partial thromboplastin time, or international normalized
ratio may be elevated in a minority of cases but appears unreliable to measure
risk of bleeding. Massive acute ingestion in suicide attempt may result in
significant anticoagulation. Single exploratory ingestion by children was not
associated with toxicity.
B. Volume and functional outcome of
ICH according to oral anticoagulant type.
In an
observational study, intracerebral hemorrhages were less severe with the newer
agents than with warfarin.
Wilson D, et
al. Neurology. 2016 Jan 26;86(4):360-6.
OBJECTIVE: To
compare intracerebral hemorrhage (ICH) volume and clinical outcome of
non-vitamin K oral anticoagulants (NOAC)-associated ICH to warfarin-associated
ICH.
METHODS: In
this multicenter cross-sectional observational study of patients with
anticoagulant-associated ICH, consecutive patients with NOAC-ICH were compared
to those with warfarin-ICH selected from a population of 344 patients with
anticoagulant-associated ICH. ICH volume was measured by an observer blinded to
clinical details. Outcome measures were ICH volume and clinical outcome
adjusted for confounding factors.
RESULTS: We
compared 11 patients with NOAC-ICH to 52 patients with warfarin-ICH. The median
ICH volume was 2.4 mL (interquartile range [IQR] 0.3-5.4 mL) for NOAC-ICH vs
8.9 mL (IQR 4.0-21.3 mL) for warfarin-ICH (p = 0.0028). In univariate linear
regression, use of warfarin (difference in cube root volume 1.61; 95%
confidence interval [CI] 0.69 to 2.53) and lobar ICH location (compared with
nonlobar ICH; difference in cube root volume 1.52; 95% CI 2.20 to 0.85) were
associated with larger ICH volumes. In multivariable linear regression
adjusting for confounding factors (sex, hypertension, previous ischemic stroke,
white matter disease burden, and premorbid modified Rankin Scale score [mRS]),
warfarin use remained independently associated with larger ICH (cube root)
volumes (coefficient 0.64; 95% CI 0.24 to 1.25; p = 0.042). Ordered logistic
regression showed an increased odds of a worse clinical outcome (as measured by
discharge mRS) in warfarin-ICH compared with NOAC-ICH: odds ratio 4.46 (95% CI
1.10 to 18.14; p = 0.037).
CONCLUSIONS:
In this small prospective observational study, patients with NOAC-associated
ICH had smaller ICH volumes and better clinical outcomes compared with
warfarin-associated ICH.
23. Caplacizumab for Acquired Thrombotic Thrombocytopenic
Purpura.
Peyvandi F,
et al. N Engl J Med. 2016 Feb 11;374(6):511-22.
BACKGROUND:
Acquired thrombotic thrombocytopenic purpura (TTP) is caused by aggregation of
platelets on ultralarge von Willebrand factor multimers. This microvascular
thrombosis causes multiorgan ischemia with potentially life-threatening
complications. Daily plasma exchange and immunosuppressive therapies induce
remission, but mortality and morbidity due to microthrombosis remain high.
METHODS:
Caplacizumab, an anti-von Willebrand factor humanized single-variable-domain
immunoglobulin (Nanobody), inhibits the interaction between ultralarge von
Willebrand factor multimers and platelets. In this phase 2, controlled study,
we randomly assigned patients with acquired TTP to subcutaneous caplacizumab
(10 mg daily) or placebo during plasma exchange and for 30 days afterward. The
primary end point was the time to a response, defined as confirmed
normalization of the platelet count. Major secondary end points included
exacerbations and relapses.
RESULTS:
Seventy-five patients underwent randomization (36 were assigned to receive
caplacizumab, and 39 to receive placebo). The time to a response was
significantly reduced with caplacizumab as compared with placebo (39% reduction
in median time, P=0.005). Three patients in the caplacizumab group had an
exacerbation, as compared with 11 patients in the placebo group. Eight patients
in the caplacizumab group had a relapse in the first month after stopping the
study drug, of whom 7 had ADAMTS13 activity that remained below 10%, suggesting
unresolved autoimmune activity. Bleeding-related adverse events, most of which
were mild to moderate in severity, were more common with caplacizumab than with
placebo (54% of patients vs. 38%). The frequencies of other adverse events were
similar in the two groups. Two patients in the placebo group died, as compared
with none in the caplacizumab group.
CONCLUSIONS:
Caplacizumab induced a faster resolution of the acute TTP episode than did
placebo. The platelet-protective effect of caplacizumab was maintained during
the treatment period. Caplacizumab was associated with an increased tendency
toward bleeding, as compared with placebo.
24. Risk of Procedural Hemorrhage
Wolfe KS, et
al. Thorax. 2 February 2016 [Epub ahead of print]
Abstract
Critically
ill and hospitalized patients often require invasive procedures as a part of
their medical care. Each procedure carries a unique set of risks and associated
complications, but common to all of them is the risk of hemorrhage. Central
venous catheterization, arterial catheterization, paracentesis, thoracentesis,
tube thoracostomy and lumbar puncture constitute a majority of the procedures
performed in hospitalized patients. We will discuss the risk factors for
bleeding complications from each of these procedures and methods to minimize
risk. The correction of coagulopathy prior to procedures is often employed by
clinicians to decrease bleeding risk, but there is minimal evidence to support
this practice.
Excerpts
CVC
The summary
evidence available at this time indicates that CVC placement carries similar
risk in patients with and without abnormalities of hemostasis. Accordingly, we
recommend the following strategies for CVC placement to minimize risk of
bleeding: 1.) presence of an experienced operator, 2.) use of real-time
ultrasound guidance for all CVC placement, … 4.) avoidance of routine
prophylactic transfusions in mild to moderate disorders of hemostasis.
LP
A recent
review of a series of studies involving both adult and pediatric populations
found that 39 LPs were performed at a platelet count less than 10,000/µL, 204
at counts between 11-20,000/0µL, 817 between 21-50,000/µL, and 858 between
51-100,000/µL. There were no bleeding complications in any of the studies.61 A
separate review found a correlation between an abnormal coagulation status and
hemorrhagic complications of LP, but it is unclear if other risk factors were
present and what constituted an abnormal coagulation status.63 Given the
paucity of data regarding optimal platelet levels for LP and the potential
risks of hematoma, consensus guidelines recommend [proceeding with the
procedure with] platelets of 50,000/µL or greater, with clinical judgment
guiding practice when platelets fall between 20-49,000/µL.61
Related
articles:
Bleeding complications of central
venous catheterization in septic patients with abnormal hemostasis. Am J Emerg Med. 2014
Jul;32(7):737-42.
The risk of spinal haematoma following
neuraxial anaesthesia or lumbar puncture in thrombocytopenic individuals. Br J Haematol. 2010;148(1):15-25.
Full-text
(free): http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2009.07899.x/full
25. Dr. Dustin Ballard’s Medically Clear: Medical findings
aren’t always true
Marin Independent Journal. 02/28/16,
4:18 PM
Perhaps you
read in the New York Times about the slew of promising anti-aging drugs in
development. Metformin (Glucophage) is one example.
Metformin has
been used since the 1920s to help control diabetics’ blood sugar levels but it
may actually do much more — perhaps prolonging life in diabetics and
non-diabetics alike. Purportedly, metformin modulates metabolism and cellular
damage through its effects on the liver controlling glucose (sugar) production.
Biologically plausible? Yes. But do I advise adding metformin to your regiment
of medications and supplements? Not so fast.
Before you
start popping metformin, or whatever trendy supplement or super food, it is
worth considering the spotty record of science’s record in discovering truth.
It’s an
unfortunate reality that many biomedical research “findings” are ultimately
proven to be illusory. This goes for drugs (remember when Vioxx was considered
a safe treatment for arthritis?), dietary associations (oat bran to prevent
heart disease?) and diagnostics (when exactly should you start getting
mammograms?) How frequently do facts become fiction? Well, sadly, quite
frequently — in fact, “findings” in medical research may be only slightly more
reliable than Donald Trump’s “facts” and only about as good as sport pundit
“expert” picks against the spread.
Feeling
doubtful? Here’s a look at the evidence behind medical evidence.
First, let’s
define what we mean by a “research finding.” A research finding is any
relationship discovered in a study that meets the criteria for statistical
significance. The typical standard for this is a “p value” of less than 0.05,
which essentially means that there is only a 1-in-20 chance that the research
finding was by chance rather than a real association. But while 95 percent
confidence in the truth of a finding may seem intuitively appealing, there’s
evidence that it may not be conservative enough.
Consider a
2005 paper by John P.A. Ioannidis, “Why most published research findings are
false.” Ioannidis builds a theoretic model of the chances of obtaining a true
research finding starting with sample size (how many patients are in the study)
and p-value. He then mixes in additional terms to account for possible
confounders that could cause a finding to be falsely true. These include
investigator bias (recognized or not); the probability, prior to study, of the
association being true, and the number of different possible associations being
tested.
From his
model, he concludes that the chances of a finding being a true finding range
from about 85 percent to lower than 20 percent! Eighty-five percent if the
study was a well-controlled randomized trial of an association with reasonably
high pre-study odds of being true; 20 percent or less if the study was
retrospective (backwards looking) and examined rather broad associations such
as diet and disease (think processed meat and cancer risk) or thousands of
associations at once (think genetic-discovery-oriented research where 30,000
genes may be tested to find 30 or so true culprits).
Subsequent
theoretic analyses have lent support to Ioannidis’ notion and generalize that
no better than 50 percent of research findings are actually correct.
Indeed, in our
recent history, there is a litany of research findings that could not be
replicated or were outright refuted, such as the Lancet’s vaccines-cause-autism
study. As such, the topic of how to distinguish the truth from the false
positive has picked up considerable steam.
If this has
you feeling skeptical about the health recommendations you receive and the
value of biomedical research, you are not alone. Fortunately, this is not a
presidential debate situation where all conclusions should be considered false
until impartially verified. There are principles that can help both researchers
and the public arrive at a better state of biomedical knowledge. And here’s
where you come in: Do not simply assume that all research follows the following
principles, be an informed consumer and learn to assess the quality of the
“findings” you hear in the news.
So, here are
those principles:
• Look for
numbers; bigger is better. The work of Ioannidis and others has demonstrated
that small numbers of observations or study subjects are more likely to have
spurious results and be non-replicable. Place more credence in studies that
have thousands, or tens of thousands of subjects rather than those with just a
handful.
• Be wary of
bias. Any studies published by entities with possible conflicts of interest or
on a topic of newsy interest have a higher chance of false findings. This is
not to say that every drug company study is rigged, but caution is advised in
interpretation.
• Perform a
“Does it makes sense?” test. The probability of a particular truth in medicine
before a study is done greatly affects the likelihood of a finding being
actually true. This principle is known as face validity. For example, just
because some people who eat a lot of ice cream are thin does not mean that ice
cream is an effective weight loss tool.
• Ask if the
findings are randomized and replicated. In 2015, there were a series of
studies, all randomized trials that demonstrated the benefit of a new clot
retrieval technique for certain types strokes. All employed the best type of
study design (randomized controlled trial) and had strongly positive results
that were repeated in multiple other separate investigations. We can believe
these results.
• Five sigma.
Different scientific disciplines use different thresholds for defining a
research finding. In medicine, the threshold is 2 sigma, which is two standard
deviations or 95 percent confidence. In physics, however, it is 5 sigma, which
equates to 99.99 percent confidence. If you see a finding in medicine that
meets this 5 sigma criteria, you better believe that Sir Isaac Newton would
approve.
So, before
you start popping metformin, or whatever trendy supplement or super food, it is
worth considering the spotty record of science’s record in discovering truth.
Fortunately, you can also take heart in the fact that science remains the most
vigorous supervisor of its own truths — false findings are discovered and
discarded, and the total body of evidence moves forwards. It may be messy, but
ultimately, it gets it right the vast majority of the time.
26. Micro Bits
A. Children may benefit from receiving
asthma meds before discharge
Children with
asthma were 78% less likely to return to the emergency department for
additional treatment within 30 days after doctors implemented a "Meds in
Hand" program at Boston Medical Center for two years. The program provides
an in-room delivery service so patients do not need to go to another pharmacy.
The study was published in Pediatrics.
B. Telemedicine project connects
non-urgent ED patients with primary care physicians
The Army is
testing a telemedicine program that connects non-emergency patients who come to
the emergency department at Blanchfield Army Community Hospital in Fort
Campbell, Ky., with primary care physicians at Eisenhower Army Medical Center
in Augusta, Ga. The program's goals include reducing ED workloads and making sure
non-emergency patients get timely access to care.
Essay: http://mhealthintelligence.com/news/army-telemedicine-pilot-targets-a-familiar-pain-point-the-er
