TAGEDNCLINICAL RESEARCH STUDY

Reducing Hospital Toxicity: Impact on Patient

Outcomes
D1X XRichard V. Milani, MD,Da,b
2X X D3X XRobert M. Bober, MD,D4Xa,b
X D5X XCarl J. Lavie, MD,D6XbX D7X XJonathan K. Wilt,D8XaX D9X XAlexander R. Milani,Da,c
10X X
D1X XChristopher J. White, MDD12X Xb

a
Center for Healthcare Innovation, Ochsner Health System; bDepartment of Cardiovascular Diseases, John Ochsner Heart and Vascular
Institute, Ochsner Clinical School University of Queensland School of Medicine, New Orleans, La; cEmory University School of Medicine,
Atlanta, Ga.

TAGEDP BSTRACT
A
BACKGROUND: Circadian rhythms are endogenous 24-hour oscillations in biologic processes that drive
nearly all physiologic and behavioral functions. Disruption in circadian rhythms can adversely impact
short- and long-term health outcomes. Routine hospital care often causes significant disruption in sleep-
wake patterns that is further compounded by loss of personal control of health information and health deci-
sions. We wished to evaluate measures directed at improving circadian rhythm and access to daily health
information on hospital outcomes.
METHODS: We evaluated 3425 consecutive patients admitted to a medical-surgical unit comprised of an
intervention wing (n = 1185) or standard control wing (n = 2240) over a 2.5-year period. Intervention
patients received measures to improve sleep that included reduction of nighttime noise, delay of routine
morning phlebotomy, passive vital sign monitoring, and use of red-enriched lighting after sunset, as well
as access to daily health information utilizing an inpatient portal.
RESULTS: Intervention patients accessed the inpatient portal frequently during hospitalization seeking per-
sonal health and care team information. Measures impacting the quality and quantity of sleep were signifi-
cantly improved. Length of stay was 8.6 hours less (P = .04), 30- and 90-day readmission rates were 16%
and 12% lower, respectively (both P
.02), and self-rated emotional/mental health was higher (69.2% vs
52.4%; P = 0.03) in the intervention group compared with controls.
CONCLUSIONS: Modest changes in routine hospital care can improve the hospital environment impacting
sleep and access to health knowledge, leading to improvements in hospital outcomes. Sleep-wake patterns
of hospitalized patients represent a potential avenue for further enhancing hospital quality and safety.
Ó 2018 Elsevier Inc. All rights reserved.  The American Journal of Medicine (2018) 131:961 966
TAGEDPKEYWORDS: Hospital toxicity; Circadian rhythm

TAGEDH1INTRODUCTIONTAGEDN condition has been called posthospital syndrome and

Recovery from hospitalization includes recuperation
from the acute illness leading to admission but also
recovery from the physiologic disruption created from
the environment of hospital care.1 This secondary
Funding: None.
Conflicts of Interest: None.
Authorship: All authors had access to the data and a role in writing the
manuscript.
Requests for reprints should be addressed to Richard V. Milani, MD,
Center for Healthcare Innovation, Ochsner Health System, 1514 Jefferson
Hwy, New Orleans, LA 70121.
E-mail address: pmaggiore@ochsner.org
has been defined as an acquired, transient period of vul-
nerability derived from the allostatic and physiologic
stress that patients experience during hospitalization.1
During hospitalization, patients are frequently deprived
of sleep, experience disruption of normal circadian
rhythms, become deconditioned, and have almost total
loss of personal control.
Sleep disruption is well documented and can impact
multiple organ systems, including immune function, coagu-
lation, physical function and coordination, cognitive perfor-
mance, and metabolism.1-3 Disruption in circadian rhythms
impacts daily cellular protein expression and can

0002-9343/© 2018 Elsevier Inc. All rights reserved.

https://doi.org/10.1016/j.amjmed.2018.04.013
962 The American Journal of Medicine, Vol 131, No 8, August 2018

significantly influence clinical outcomes, from timing of bedside to provide nursing staff an alternative to standard
wound healing to surgical outcomes.4-6 white lights when performing nighttime assessments. Vital
Loss of personal control is common during hospitaliza- signs including heart rate, blood pressure, respirations, tem-
tion and is so profound that being a hospital patient has perature, and oxygen saturation were collected passively
been called ‘one of the most disempowering situations one and unobtrusively using U.S. Food and Drug Administra-
can experience in modern society.’7,8 In a survey of hospital tion approved wireless technology worn on the wrist (ViSi
patients, 90% of respondents wanted to review their hospi- Mobile, Sotera, San Diego, Calif) that recorded data directly
tal medication list, but only 28% to the electronic medical record
were given the opportunity.8,9 In Clinical Significance (Epic Systems Corporation, Verona,
another study, only 32% of patients Wis) at 1-minute intervals.13,14
could correctly name even one of  Circadian rhythms control many physi- Nursing was alerted to vital signs
their hospital physicians.8,10 ologic and behavioral functions. that were considered abnormal via
The purpose of this investigation machine-to-nurse secure messaging
was to examine the impact of inter-
 Routine hospital care commonly is dis- via Sotera’s Insight app to an iPhone
ventions focused on improvements ruptive to a patient’s intrinsic circa- (Apple Inc, Cupertino, Calif) carried
in the quality and quantity of sleep dian rhythm, which is further by each nurse.
as well as enhancing the patient’s compounded by loss of personal con- Each patient received an iPad
control and understanding of trol of health information. (Apple Inc.) on admission, enabled
healthcare knowledge and deci- with the inpatient portal, MyChart
 Modest changes in hospital routines
sions. The outcomes evaluated Bedside (Epic Systems Corpora-
included length of stay, hospital can be implemented that reduce circa- tion). The Health Insurance Porta-
readmission, intensive care unit dian disruption and enhance free flow bility and Accountability Act secure
(ICU) transfers, and subjective of information to patients. app identifies the patient’s treatment
measures of well-being.  These changes result in measurable team and includes pictures as well
as brief bios of each provider and
improvements in hospital length of nurse rendering care to the patient.
TAGEDH1METHODSTAGEDN stay, readmission, and subjective The app also provides detailed
We prospectively evaluated hospital measures of satisfaction. information about the patient’s
outcomes in 3425 consecutive car- active medications; education on
diovascular patients admitted to the acute illness under treatment;
available beds on a medical-surgical daily results of labs, radiology, and vital signs; and the
floor consisting of a 15-bed intervention wing (n = 1,185) or schedule of diagnostic tests planned for the day. Patients
a standard 37-bed control wing (n = 2240). All patients were could record conversations with their attending physician
admitted to noncritical care beds capable of telemetry when during rounds for playback later for themselves or family
ordered, and bed selection was based solely on bed avail- members who may not have been present.
ability; bed control had no insight into the care delivery pro- Subjective measures were assessed using the Hospital
cess in either wing. The control wing received standard of Consumer Assessment of Healthcare Providers and Sys-
care as per hospital routine. tems following discharge. Disease burden was assessed
The intervention wing utilized specific measures to using the age-adjusted Charlson comorbidity index, with
improve sleep patterns including the monitoring and reduc- higher scores indicating greater comorbidity.15,16
tion of nighttime noise, delay of routine morning phlebot- Statistical analysis was performed using SPSS version
omy, and use of red-spectrum lighting after sunset during 16.0 (SPSS Inc., Chicago, Ill). Results are expressed as
routine nighttime checks.11,12 Noise levels were monitored mean standard deviation, or as n (%) where appropriate.
in hospital corridors outside patients’ rooms, and a silent Analysis of differences between groups was performed
visual notification system was displayed in hallways to hos- using Student’s t test for continuous variables and the chi-
pital personnel when noise levels after hours exceeded squared test for categorical variables. Median comparisons
65 dB, which corresponded to approximately 30 dB in were made using the Mann-Whitney test.
patient rooms with the door closed. Total nighttime noise
burden was defined as the duration of time (minutes) when
the decibel level exceeded 65 dB. Laboratory services were TAGEDH1RESULTSTAGEDN
instructed to delay all routine phlebotomy (nonstat, non- The study cohort consisted of 3425 consecutive patients
timed) until after 6:00 AM. Reports outlining each of these from March 2015 to October 2017. The mean age of the
measures were provided each morning and evening to hospi- study cohort was 64 § 16 years, 57% were male, and geo-
tal care teams, and feedback was solicited to identify issues metric mean length of hospital stay was 5.9 days (142
(ie, any source of noise) with recommendations on methods hours). The median Charlson index score was 6.0. Admit-
to eliminate disturbances that could impact sleep quality. ting services included cardiology (41.5%), hospital medi-
An additional red-spectrum light was installed near the cine (31.8%), heart failure/heart transplant (22.0%), and
Milani et al Reducing Hospital Toxicity 963

Table 1 Demographics of the Intervention and Control Groups body mass index, or Charlson index score when compared
Characteristic Intervention Control P Value with controls (Tables 1 and 2).
(n = 1185) (n = 2240) Inpatient portal use was frequently engaged, utilized in
70% of patients, with the average patient accessing infor-
Age (years) 66.2 § 15.2 63.2 §16.1 <.001
Males (%) 56.7% 58.4% .34 mation multiple times during hospitalization. The most fre-
Black (%) 38.5% 40.0% .39 quent option assessed was review of individual health
White (%) 59.2% 57.3% .30 metrics (labs, vitals, etc.), followed by care team informa-
Hispanic (%) 1.1% 1.7% .17 tion, schedule of diagnostics/procedures, medication
Charlson index (median) 6.0 6.0 .70 administration details, and patient-prescribed education
Creatinine (mg/dL) 1.5 §1.4 1.4 §1.3 .52 (Table 3).
Body mass index (kg/m2) 29.2 §8.0 29.3 §7.6 .63 Table 4 compares outcome measures between patients in
each of the two groups. The intervention was successful in
improving measures that impact sleep quality and duration;
Table 2 Age-Adjusted Charlson Comorbidity Score Distributions nighttime noise burden fell by 31% (P = .04), and phlebot-
Between Intervention and Control Groups omy time delay provided the opportunity for an additional
Charlson Index Control Intervention P Value 1.2 hours of sleep (P < .001). Hospital length of stay aver-
aged 8.6 hours less in the intervention group ( 6%,
0-1 5.3% 5.1% .76
2-3 16.2% 14.5% .19 P = .04), whereas mortality and clinical deterioration
4-5 19.7% 21.4% .23 requiring ICU transfer remained unchanged. Both 30- and
6-7 22.4% 21.4% .51 90-day readmission was significantly lower in the interven-
8 36.5% 37.6% .52 tion group ( 16%, P = .02 and 12%, P = .009, respec-
tively), and patients with two or more hospital admissions
90 days after discharge trended lower ( 14%, P = .06).
Patient-reported measures rating emotional/mental health
Table 3 Average Usage of the Inpatient Portal (Epic MyChart as ‘very good or excellent’ were higher (+32%, P = .03),
Bedside) per Admission and the need for medicine to treat pain trended lower
Activity Frequency per ( 38%, P = .07) in the intervention group.
Admission We further evaluated the clinical impact of the interven-
Review health metrics 0.62
tion based on tertiles of Charlson scores (Table 5). There
Obtain care team information 0.58 were no differences in mortality, ICU transfers, and length
Load schedule of upcoming diagnostics 0.51 of stay between intervention and control patients within
Get medication administration details 0.50 each Charlson group. However, there were significant differ-
View patient prescribed education 0.45 ences in both 30- and 90-day readmission rates in patients
with Charlson scores < 5. Compared with controls, inter-
vention patients demonstrated a 34% reduction in 30-day
readmission (17.9% vs 11.8%, P = .01) and a 33% reduction
surgery (3.2%), with the remaining 1.5% being various
in 90-day readmission (30.7% vs 20.7%, P < .001).
other services. Hospital physicians were surveyed, and
there were no reported delays or alterations in workflow as
a result of the intervention. TAGEDH1DISCUSSIONTAGEDN
The intervention cohort was slightly older (mean age There are several key findings from this investigation. First,
66.2 § 15.2 vs 63.2 § 16.1 years, P < .001), but there were provided the opportunity, the majority of patients and their
no other significant differences in sex, race, creatinine, families will access information to better identify members

Table 4 Outcome Measures in Intervention and Control Groups

Parameter Control Intervention Change P Value
Night noise burden (minutes) 60.3 § 398.2 41.7 § 335.3 31% .04
Morning phlebotomy time (mean) 4:53 AM 6:04 AM 1:11 <.001
Hospital length of stay (hours) 145.1 § 190.2 136.5 § 144.4 6% .04
Intensive care unit transfer 9.9% 8.4% 15% .16
Inpatient mortality 0.7% 0.7% 0% .99
30-day readmission 22.4% 18.8% 16% .02
90-day readmission 39.0% 34.5% 12% .009
2 admissions over 90 days 17.3% 14.9% 14% .06
Emotional/mental health 52.4% 69.2% 32% .03
(rating ‘very good/excellent’)
Medicine needed for pain (rating) 53% 33% 38% .07
964
Table 5 Differences in Outcomes Between Intervention and Control Patients Based on Charlson Score
Charlson Score 30-Day Readmission 90-Day
Control Interv P Control
<5 (n = 1061) 17.9% 11.8% .01 30.7%
5-7 (n = 1102) 20.9% 19.8% .69 38.5%
8 (n = 1262) 27.5% 23.6% .13 46.5%
Interv = intervention.
of their care team and details about their ongoing medical
status including active medications, upcoming schedule of
diagnostic testing, and recent test results. Second, improve-
ments in the conditions for sleep, as well as measures to
enhance personal control of healthcare knowledge, can be
easily implemented in the routine environment of hospital
care without significant disruptions in operational work-
flows. Finally, interventions designed to enhance personal
control of health information and improve intrinsic circa-
dian rhythms can lead to significant improvements in clini-
cal outcomes (rehospitalization), operational measures
(length of stay), and patient well-being.
The role of chronobiology in health is generally under-
appreciated during routine hospital care; however, circa-
dian rhythms have been demonstrated to modulate a wide
range of health effects. More than 43% of all protein coding
genes are regulated by the circadian clock, thus influencing
multiple physiologic parameters including immune func-
tion, blood pressure, hormone production, efficacy of medi-
cation, wound healing, and surgical outcomes.2,4,17,18 For
instance, influenza vaccination administered to elderly
patients in the morning generates a significantly greater
antibody response than does afternoon vaccination.19 Burn
injuries suffered in the daytime heal significantly faster
than similar injuries incurred at night.5 Aortic valve surgi-
cal patients experience better clinical outcomes when sur-
gery is performed in the afternoon rather than in the
morning.6
Acute and chronic disruption of circadian rhythm has
also been linked to a wide range of adverse health out-
comes. Chronic shift work is known to increase the risk for
diabetes, gastrointestinal disorders, cardiovascular disease,
lipid disorders, and cancer such that, in 2007, the World
Health Organization (WHO) declared shift work a carcino-
gen.2,20-22 The acute effects of just a 1-hour change in day-
light savings time include an increase in myocardial
infarction, stroke, automobile accidents, and accidents with
fatalities.23-26 Yet despite a growing body of evidence dem-
onstrating the relevance of circadian functions in daily
health, routine hospital care often results in major and often
unnoticed disruptions of the sleep-wake cycle.
In this study, control patients underwent daily phleboto-
mies during sleeping hours as part of routine hospital care
and, not uncommonly, vital sign assessments. Although
this may be necessary for clinical care in specific cases,
most noncritical patients can have these procedures per-
formed exclusively during waking hours. There were no
The American Journal of Medicine, Vol 131, No 8, August 2018
Readmission Length of Stay (hours)
Interv P Control Interv P
20.7% <.001 134.8 § 145.2 133.0 § 178.4 .87
34.2% .16 154.9 § 217.7 145.9 § 220.7 .52
45.8% .82 145.2 § 198.0 131.3 § 145.1 .16
adverse clinical consequences from delaying routine phle-
botomy until after 6:00 AM in the intervention group, and
vital signs were comfortably obtained nonobtrusively and
noninvasively through the night using currently available
technology.
Additionally, a more subtle form of circadian disruption
can take place when checking patients after hours using
standard lighting.11,12 When exposed to even small
amounts of white light (blue and blue-green), intrinsically
photosensitive retinal ganglion cells (ipRGCs) signal the
suprachiasmatic nucleus to reset circadian clocks, thus
altering timed expression of numerous biologic events.27-30
The ipRGCs are most sensitive to short-wavelength blue
and blue-green light, and are less sensitive to red or orange-
enriched light.20,30 By substituting blue-enriched light with
red-enriched light after hours, we likely blunted stimulation
of ipRGCs, thus reinforcing intrinsic circadian rhythms.
Hospital noise is also a contributing factor for sleep dis-
ruption, and elevated levels of hospital noise are directly
correlated to sleep loss.31-33 Hospital noise has been
reported as high as 67 dB in the ICU and 42 dB in medical
and surgical wards, far exceeding the 30 dB nightly target
for patient rooms recommended by the WHO.32,34 Our
intervention included sound monitoring with silent alerts to
hospital personnel when in-room noise levels exceeded the
WHO recommended levels. Additionally, daily feedback
from care teams led to workflow changes that resulted in
progressive reduction in the overall nightly noise burden.
These measures taken together enhanced the conditions for
better sleep health, creating a true patient-centered environ-
ment of care.7,35,36
Engaging patients in their healthcare has recently
become a focus of great interest.37 The Institute of Medi-
cine recommends that patients have access to a ‘free flow
of information’ and clinical knowledge, enabling them to
be the ‘source of control’ in making healthcare decisions.7,8
This has never been more important than in the hospital set-
ting, which can be an unfamiliar and isolating environment
filled with anxiety and unanswered questions, and described
as ‘one of the most disempowering situations one can expe-
rience in modern society.’8 Hospitalized patients experi-
ence significant knowledge gaps and desire greater
understanding of their clinical status, medications, and care
team information, but only a minority of patients are pro-
vided the opportunity to close these gaps.8-10 In contrast,
efforts that augment transparency and flow of information
led to enhanced patient satisfaction and improved clinical
Milani et al Reducing Hospital Toxicity
outcomes including a reduction in readmission.8,38,39 Our
intervention resulted in higher levels of emotional and men-
tal health as measured by the Hospital Consumer Assess-
ment of Healthcare Providers and Systems as well as
improvement in clinical outcomes. Although our study
incorporated several interventions simultaneously, enhanc-
ing personal control likely contributed to the overall
improvements described.
Finally, we demonstrated that the intervention reduced
30- and 90-day readmission primarily in patients with lower
Charlson scores. There are two possible explanations for
this finding. First, it is possible that the intervention was
strong enough to blunt the effects of hospital toxicity in
patients with less comorbidity but was less effective in
overcoming these adverse effects in patients with a greater
burden of illness and thus susceptibility. Second, it may
indicate that the underlying pathology of multiple comor-
bidities is the primary driver of readmission, diminishing
the additional impact imposed from the environment of
hospitalization.
This study has several limitations worth noting. First,
this was not a randomized trial. Patients were allocated to
either group based solely on bed availability as per routine
hospital practice, and the investigators had no influence on
bed or group assignment. However, because of the large
sample size and minimal differences identified between
groups at baseline, we feel that the outcomes were not
biased. Second, this was performed at a single site, and
other investigators should confirm our results. Finally, we
applied two important interventions simultaneously
(enhancement of sleep and personal control), and our out-
comes reflect the effects of the combined intervention.
In summary, modest patient-centered interventions that
focus directly on enhancing access to health knowledge in
conjunction with improvements in the hospital environment
impacting sleep quality can be easily incorporated in mod-
ern hospital practice and lead to meaningful improvements
in quality, safety, cost, and patient satisfaction.
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