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”
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
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
Mansi I, Mortensen EM. Mortality After Perioperative β-Blocker Use in Noncardiac Surgery. JAMA 2013; 310(6): 645-646
London MJ, Schwartz GG, Henderson WG. Mortality After Perioperative β-Blocker Use in Noncardiac Surgery—Reply. JAMA 2013; 310(6): 646
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
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.
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
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
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.
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
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
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 “”). Inouye et al () 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 “”
· 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”
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
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
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
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:
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