In our May 2013 What’s
New in the Patient Safety World column “Beta
Blocker Debate Just Won’t Go Away” we joked that one
pro-beta-blocker article always engenders another anti-beta-blocker article and
vice versa! You guessed it – here’s more!
Most of you recall the history of the debate. After several
years in which we pushed for almost universal use of beta blockers perioperatively, publication of the POISE trial (Devereaux
2008) significantly changed things. The POISE trial showed that,
though preoperative beta blockers prevented 15 MI’s for every 1000 patients
treated, there was an increased risk of stroke and an excess of 8 deaths per
1000 patients treated. Largely since that time recommendations have been to
continue beta blockers in the perioperative period in patients previously
taking them but most no longer begin them perioperatively
in patients not previously taking them.
But there have been numerous criticisms of the POISE trial.
Specifically, patients received fairly large doses of metoprolol
shortly before their surgery and many have argued that starting beta blockers
well in advance of surgery and titrating the dose slowly would not have
produced the adverse outcomes seen in POISE.
In the interim, serious questions about the conduct and
validity of several prior studies supporting the use of perioperative beta
blockers have been raised (see the new study by Bouri
et al. discussed below).
A number of retrospective observational studies had
suggested that there might be a benefit from perioperative beta blockers in
some cases. The most recent observational study again that we discussed in our May 2013 What’s New in the Patient Safety
World column “Beta
Blocker Debate Just Won’t Go Away” raised the question of utility of
perioperative beta blockers in patients undergoing noncardiac
surgery. That study (London 2013)
found that among propensity-matched control patients undergoing noncardiac, nonvascular surgery, perioperative
β-blocker exposure was associated with lower rates of 30-day all-cause
mortality in patients with 2 or more Revised Cardiac Risk Index factors. But
even that study has been questioned regarding potential bias due to the
methodology used (see Mansi 2013 and the reply by London 2013b).
Because of the issues surrounding the series of pro-beta-blocker
studies, a new meta-analysis of beta-blockade in non-cardiac surgery was
undertaken excluding the discredited studies (Bouri
2013). The conclusion of that meta-analysis was that beta-blockade
caused a 27% increase in all-cause
mortality. While the rate of non-fatal MI was significantly reduced in that
meta-analysis the rates of stroke and hypotension were increased in addition to
the increased mortality rates. Note that the meta-analysis was dominated by the
large POISE trial already mentioned above. Note also that the authors rebut
some of the criticisms of the POISE trial related to dose and titration. The
authors call for various specialty societies to revise their guidelines
regarding beta-blockade in non-cardiac surgery until further randomized
controlled trials are done.
We concur that the controversy is unlikely to go away until
a large randomized controlled trial is undertaken using a beta-blockade regimen
that everyone can agree upon.
Our prior columns on
perioperative use of beta blockers:
November 20, 2007 “New
Evidence Questions Perioperative Beta Blocker Use”
November 4, 2008 “Beta
Blockers Take More Hits”
December 2009 “Updated
Perioperative Beta Blocker Guidelines”
November 2010 “More
Perioperative Beta Blocker Controversy”
November 2012 “Beta
Blockers Losing Their Luster?”
May 2013 “Beta
Blocker Debate Just Won’t Go Away”
References:
Devereaux PJ, Yang H, Yusuf S, et
al for the POISE Study Group. Effects of extended-release metoprolol
succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet 2008; 371(9627):
1839-1847
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2808%2960601-7/fulltext
London MJ, Hur K, Schwartz GG,
Henderson WG. Association of Perioperative β-Blockade With
Mortality and Cardiovascular Morbidity Following Major Noncardiac
Surgery. JAMA 2013; 309(16): 1704-1713
http://jama.jamanetwork.com/article.aspx?articleid=1681412
Mansi I, Mortensen EM. Mortality After Perioperative β-Blocker Use in Noncardiac Surgery. JAMA 2013; 310(6): 645-646
http://jama.jamanetwork.com/article.aspx?articleid=1728707
London MJ, Schwartz GG, Henderson WG. Mortality After Perioperative β-Blocker Use in Noncardiac Surgery—Reply. JAMA 2013; 310(6): 646
http://jama.jamanetwork.com/article.aspx?articleid=1728709
Bouri S, Shun-Shin MJ, Cole GD, Mayet J, Francis DP. Meta-analysis of secure randomised controlled trials of β-blockade to prevent
perioperative death in non-cardiac surgery. Heart 2013; Published Online First: 31 July 2013 doi:10.1136/heartjnl-2013-304262
http://heart.bmj.com/content/early/2013/07/30/heartjnl-2013-304262.full.pdf+html
Print “September
2013 More Perioperative Beta-Blocker Controversy”
An interesting new
study (Harley
2013) has raised the question as to
whether mortality of dialysis patients may be higher when the caseload of their
nephrologist is higher. The authors retrospectively reviewed a cohort of
patients receiving dialysis through facilities of one for-profit provider in an
urban area of California. They found in demographic characteristic–adjusted
analyses that each 50-patient increase in caseload was associated with a 2%
increase in patient mortality risk (hazard ratio, 1.02; 95% confidence
interval, 1.00 to 1.04; P<0.001). Also, patients treated by nephrologists
with the lowest patient mortality rates received higher dialysis doses, had
longer sessions, and received more kidney transplants.
The study
conclusions are limited by the fact that this was one population and the study
lacked important details about severity of illness and other patient level
factors that might be important in terms of mortality. Nevertheless, the study
does raise an important question that should lead to further investigation.
The study comes on
the heels of another study (Kawaguchi
2013) that linked mortality of dialysis patients to the amount of physician
contact they had. That study, using data from the large international Dialysis Outcomes and Practice Patterns Study
(DOPPS), found an inverse correlation between the frequency of
patient-doctor contact and all-cause mortality. They also found that
each 5-minutes-shorter duration of patient-doctor contact was associated
with a 5% higher risk for death, on average, after adjusting for visit
frequency and other covariates. There were also modest inverse associations
between both patient-doctor contact frequency and duration with hospitalization
but not with kidney transplantation.
While there have
been many conditions that have linked physician (or center) experience, usually
measured by volume of cases, to better outcomes, most of those have been
surgical conditions. There have been fewer studies on caseload and mortality
for medical conditions.
But we have seen
“J-shaped” mortality curves in the past. At one time when we were looking a
bariatric surgery mortality rates in New York State we found that mortality
rates declined when a surgeon or center did between 50 and 100 cases. However,
interestingly, there seemed to be an increase in mortality once the 250 case
level was reached. We were unable to tell at that time whether that meant the
surgeons and centers had become too busy or simply that, because of their
experience, they were getting more complex cases. We suspected the latter. We
don’t know whether that observation has held up over the years or not.
Given the
complexities of dealing with all the comorbidities in dialysis patients it
would not be at all surprising that more patient-physician contact might be
associated with better outcomes. But at this point, the observations in these
two studies are merely hypothesis-generating and merit further prospective
studies.
References:
Harley KT, Streja E, Rhee CM, et
al. Nephrologist Caseload and Hemodialysis Patient Survival in an Urban Cohort.
J Am Soc Neprhology 2013; August 8, 201310.1681/ASN.2013020123
http://jasn.asnjournals.org/content/early/2013/08/06/ASN.2013020123.abstract
Kawaguchi T, Karaboyas A, Robinson
BM, et al. Associations of frequency and duration of patient-doctor contact in
hemodialysis facilities with mortality. J
Am Soc Nephrol 2013;
July 25, 2013 DOI: 10.1681/ASN.2012080831
http://jasn.asnjournals.org/content/early/2013/07/23/ASN.2012080831.abstract
Print “September
2013 Is Nephrologist Caseload Related to Dialysis Mortality?”
A number of years
ago quality improvement staff at a hospital proudly showed me their C-section
and VBAC (vaginal birth after previous C-section) rates for the first 6 months
of the year which showed dramatically lower rates for both compared to the
previous year. I told them “show me the same data in September”. Of course, I
knew from previous experience that the rates would likely jump substantially in
July and August, mostly due to scheduled vacations for both physicians and
families. Sure enough, the September report showed that the C-section and VBAC
rates through the end of August were now the same as the prior year.
Cesarean section
rates remain at high levels throughout the US. Now a new study (Iriye
2013) has suggested that a full-time laborist
model has resulted in reduced cesarean section rates whereas a community laborist model did not. The study was a retrospective
before and after study at a tertiary hospital staffed by private practice
physicians, broken up into three time periods from 2006 to 2011. The first
period was 16 months during which there were no laborists.
The second a 14-month period where a community laborist
model was used. And the final period 24 months with full-time laborists. C-section rates for the three periods were
39.2%, 38.7%, and 33.2%, respectively.
Because this is a
retrospective study, not a controlled trial, one has to be careful that factors
other than the full-time laborist program were not
contributory. The obvious one would be the recent campaign to reduce non-medically
indicated labor inductions and C-sections prior to 39 weeks of pregnancy (see
our February 8, 2011 Patient Safety Tip of the Week “Inducing
Too Early”). That campaign, originally sponsored by the March of Dimes,
Leapfrog Group, California Maternal Quality Care Collaborative and the
California Department of Public Health; Maternal, Child and Adolescent Health
Divisions, and later adopted by the American College of Obstetricians and
Gynecologists (ACOG) highlighted the risks to newborns delivered prior to 39
weeks of gestation and provided tools to help avoid inductions prior to 39
weeks.
In fact, recently
released CDC data (Osterman 2013) shows that the C-section rate in the US has leveled off from 2009 to 2011
after 12 years of consecutive increases. Interestingly, C-section delivery
rates decreased more than 5% among births at 38 weeks of gestation, but
increased 4% among births at 39 weeks. This probably does reflect the campaign
noted above.
Nevertheless, we do
suspect that much of the success in the Iriye
study was due to the full-time laborist model. That
model is getting increasing traction at many hospitals and is worth your
looking at. And, of course, by now you should all be onboard for the 39-week
campaign.
References:
Iriye BK, Huang WH, Condon J, et
al. Implementation of a laborist program and
evaluation of the effect upon cesarean delivery. American Journal of Obstetrics & Gynecology 2013; published
online 30 July 2013
http://www.ajog.org/article/S0002-9378%2813%2900656-X/abstract
Osterman MJK, Martin JA. Changes in Cesarean Delivery
Rates by Gestational Age: United States, 1996–2011. CDC 2013; NCHS Data Brief Number
124, June 2013
http://www.cdc.gov/nchs/data/databriefs/db124.htm
Print “September
2013 Full-Time Laborists Reduce C-Section Rates”
We’ve done multiple columns on delirium in ICU patients and
post-op patients (see the list at the end of today’s column) and have focused
on identification of patients at risk for delirium and interventions to prevent
delirium or mitigate delirium when it does occur. Most interventions have been nonpharmacological. Nevertheless, use of haloperidol in
attempt to prevent delirium or modify its course and severity is still common
in hospitals despite lack of convincing evidence of its effectiveness.
Now a new randomized controlled trial has demonstrates no
impact from early treatment with haloperidol on mechanically ventilated ICU
patients (Page
2013). The authors randomized adult ICU patients within 72 hours of ICU
admission to either IV haloperidol or placebo. They found no significant
difference between the two groups in number of days without delirium or coma,
mortality, ICU length of stay, hospital length of stay, or time on ventilator.
Though there appeared to be no serious side effects of treatment, there really
were no beneficial effects seen.
In an editorial
accompanying the article Skrobik raises the issue of
whether we should be looking to treat delirium pharmacologically at all,
noting that only nonpharmacological measures have
been shown to reduce delirium in critically ill patients (Skrobik
2013).
However, in many of
our prior columns on delirium we have mentioned multimodality intervention
programs that were promising in reducing the incidence or severity of delirium
in hospitalized patients (see our Patient Safety Tips of the Week for October
21, 2008 “Preventing
Delirium”, October 14, 2009 “Managing
Delirium”, February 10, 2009 “Sedation
in the ICU: The Dexmedetomidine Study”, March 31,
2009 “Screening
Patients for Risk of Delirium” and January 26, 2010 “Preventing
Postoperative Delirium”). One of those interventions was HELP, the Hospital
Elder Life Program (see our October 21, 2008 Patient Safety Tip of the Week “Preventing
Delirium”). Inouye et al (Inouye
1999) had shown in a
landmark study of 852 medical patients aged 70 and older that management of 6
risk factors was able to reduce the incidence of delirium from 15% to 9.9%. The
number of days with delirium and the number of episodes of delirium was also
reduced by the intervention. The intervention targeted cognitive impairment,
sleep deprivation, immobility, visual impairment, hearing impairment, and
dehydration. This was strong evidence that a multicomponent intervention could
be of benefit in reducing delirium.
However, getting physicians to use those interventions has
been difficult. So recently researchers in Indiana looked at whether a clinical
decision support system could reduce the occurrence of delirium by avoiding unnecessary
urinary catheters and physical restraints, consulting geriatricians, and
avoiding anticholinergic drugs (Khan 2013).
In 60 adults with cognitive impairment who were part of a larger study on
patients transferred to an ICU they found that there was no significant
difference between the intervention group and the control group in the
discontinuation of urinary catheters or physical restraints, orders for
geriatric consultation, discontinuation of anticholinergic drugs, or the
incidence of delirium. They conclude that use of a computer-based clinical decision support system may not be
effective in changing prescribing patterns or in decreasing the incidence of
delirium.
Though the results of the clinical decision support system
on preventing delirium were disappointing, we hope this does not deter you from
implementing multimodality intervention programs in patients at risk for
delirium. Nursing care plans, standardized order sets, HELP programs, comprehensive
geriatric care programs, clinical pharmacist programs, and other interventions
may be better ways to address the issue rather than using computerized decision
support systems. We know that many of our most well intended clinical decision
support tools fail because of alert fatigue. Maybe the alerts generated by such
systems need to go to someone other than the physician. For example, if
patients can be flagged as being at risk for delirium from data within the
electronic medical record an alert could go to nursing personnel or a clinical
pharmacist and they may be successful at getting our physicians to do the
interventions.
Some of our prior
columns on delirium assessment and management:
·
October
21, 2008 “Preventing
Delirium”
·
October
14, 2009 “Managing
Delirium”
·
February
10, 2009 “Sedation
in the ICU: The Dexmedetomidine Study”
·
March
31, 2009 “Screening
Patients for Risk of Delirium”
·
June 23,
2009 “More
on Delirium in the ICU”
·
January
26, 2010 “Preventing
Postoperative Delirium”
·
August
31, 2010 “Postoperative
Delirium”
·
September
2011 “Modified
HELP Helps Outcomes in Elderly Undergoing Abdominal Surgery”)
·
December
2010 “The
ABCDE Bundle”
·
February
28, 2012 “AACN
Practice Alert on Delirium in Critical Care”
·
April 3, 2012 “New
Risk for Postoperative Delirium: Obstructive Sleep Apnea”
·
August
7, 2012 “Cognition,
Post-Op Delirium, and Post-Op Outcomes”
References:
Page VJ, Ely EW, Gates S, et al. Effect
of intravenous haloperidol on the duration of delirium and coma in critically
ill patients (Hope-ICU): a randomised, double-blind,
placebo-controlled trial. The Lancet Respiratory Medicine 2013; Early Online
Publication 21 August 2013 doi:10.1016/S2213-2600(13)70166-8
http://www.thelancet.com/journals/lanres/article/PIIS2213-2600%2813%2970166-8/fulltext
Skrobik Y. Can critical-care
delirium be treated pharmacologically? Lancet Respir
Med 2013; Early Online Publication, 21 August 2013 doi:10.1016/S2213-2600(13)70178-4
http://www.thelancet.com/journals/lanres/article/PIIS2213-2600%2813%2970178-4/fulltext
Inouye SK, Bogardus ST, Charpentier PA, Leo-Summers L, Acampora
D, Holford TR, Cooney LM. A Multicomponent
Intervention to Prevent Delirium in Hospitalized Older Patients. NEJM 1999;
340: 669-676
http://content.nejm.org/cgi/reprint/340/9/669.pdf
Khan BA, Calvo-Ayala E, Campbell
N, et al. Clinical Decision Support System and Incidence of Delirium in
Cognitively Impaired Older Adults Transferred to Intensive Care. Am J Crit Care 2013; 22(3): 257-262
http://ajcc.aacnjournals.org/content/22/3/257.abstract
Print “September
2013 Disappointing Results in Delirium”
ISMP has just
identified another tragedy related to fentanyl patches and has issued an appeal
for all providers to take action to prevent similar incidents (ISMP
2013). We’ve written frequently about the dangers of fentanyl, especially
fentanyl patches (see the list at the end of today’s column).
The new case
identified by ISMP involved a 15-month old baby who was cuddling with his
mother while both napped. The mother was wearing a fentanyl patch on her chest
at the time. When she awakened the baby was unresponsive and the patch missing.
The child was taken to a hospital but could not be resuscitated and died. The
presumption was that the baby had ingested the patch.
This is but one in a
tragic series of similar events regarding accidental deaths due to contact with
or ingestion of fentanyl patches. ISMP notes we are all guilty of “bystander
apathy” when we see such cases and assume that someone else will fix the
problem. They call for increased efforts on the parts of physicians, nurses,
pharmacists, hospitals, professional organizations, safety organizations,
pharmaceutical companies, the FDA, and licensing and accrediting organizations
to raise awareness of this serious issue.
The ISMP
article above has links to their free patient education checklist and
consumer leaflet plus links to several FDA resources to help with education
around safety of fentanyl patches. ISMP stresses that no patient should ever be
allowed to walk out of a doctor’s office, hospital, clinic or pharmacy without
face-to-face instructions on the use and safety issues surrounding fentanyl
patches.
The recent ISMP
article reiterates many of the previous cases and has an excellent discussion
on pharmacodynamics of the fentanyl patches based upon the mode of exposure.
They note that the patches are designed for slow absorption through the skin
over 72 hours but that ingestion of patches leads to much more rapid absorption
via the buccal route, resulting in very high blood
and tissue fentanyl levels. Chewing the patch leads to even higher levels. And
they note that even used patches (i.e. those already worn for 72 hours)
may still contain very significant amounts of drug.
Children,
particularly those under the age of 2, have been especially prone to
accidentally ingest or otherwise absorb fentanyl from such patches. Note also
that pets are vulnerable. So the educational piece must involve information not
only about use of fentanyl patches but also about safe storage and disposal.
Our September 13,
2011 Patient Safety Tip of the Week “Do
You Use Fentanyl Transdermal Patches Safely?” and our May 2012 What’s New
in the Patient Safety World column “Another
Fentanyl Patch Warning from FDA” had numerous recommendations regarding
what you should be doing to improve safety of fentanyl patches.
We strongly
encourage you to make all in your organization aware of the issue and the
availability of these educational resources for your staffs and patients and
families. ISMP has always taken the lead on this issue but we can no longer let
them carry the ball themselves. It’s all or our responsibilities to prevent
another tragedy from occurring.
Fentanyl patches
should be one of your high alert medications. If you are looking for a topic
around which to conduct a FMEA (failure mode and effects analysis) you can’t
beat this one for identifying multiple areas of potential vulnerability.
Some of our other Patient Safety Tips of the Week
regarding fentanyl and fentanyl patches:
References:
ISMP (Institute for Safe Medication Practices). FentaNYL patch fatalities linked to “bystander apathy”. We
ALL have a role in prevention! ISMP Medication Safety Alert! Acute Care Edition
2013. August 8, 2013
http://www.ismp.org/Newsletters/acutecare/showarticle.asp?id=55
Print “September
2013 ISMP Outreach on Fentanyl Patch Safety”
Print “September
2013 What's New in the Patient Safety World (full
column)”
Print “September
2013 More Perioperative Beta-Blocker Controversy”
Print “September
2013 Is Nephrologist Caseload Related to Dialysis Mortality?”
Print “September
2013 Full-Time Laborists Reduce C-Section Rates”
Print “September
2013 Disappointing Results in Delirium”
Print “September
2013 ISMP Outreach on Fentanyl Patch Safety”
Print “September
2013 What's New in the Patient Safety World (full
column in PDF version)”
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