Effect of Earplugs during The Night on The Onset of Delirium and Sleep Perceptiona: Randomised Controlled Trial in Intensive Care Patients

ABSTRACT

Van Rompaey B, Elseviers MM, Van Drom W, Fromont V, Jorens PG

INTRODUCTION: This study hypothesised that a reduction of sound during the night using earplugs could be beneficial in the prevention of intensive care delirium. Two research questions were formulated. First, does the use of earplugs during the night reduce the onset of delirium or confusion in the ICU? Second, does the use of earplugs during the night improve the quality of sleep in the ICU?

METHODS: A randomized clinical trial included adult intensive care patients in an intervention group of 69 patients sleeping with earplugs during the night and a control group of 67 patients sleeping without earplugs during the night. The researchers were blinded during data collection. Assignment was performed by an independent nurse researcher using a computer program. Eligible patients had an expected length of stay in the ICU of more than 24 hours, were Dutch- or English-speaking and scored a minimum Glasgow Coma Scale of 10. Delirium was assessed using the validated NEECHAM scale, sleep perception was reported by the patient in response to five questions.

RESULTS: The use of earplugs during the night lowered the incidence of confusion in the studied intensive care patients. A vast improvement was shown by a Hazard Ratio of 0.47 (95% confidence interval (CI) 0.27 to 0.82). Also, patients sleeping with earplugs developed confusion later than the patients sleeping without earplugs. After the first night in the ICU, patients sleeping with earplugs reported a better sleep perception.

CONCLUSIONS: Earplugs may be a useful instrument in the prevention of confusion or delirium. The beneficial effects seem to be strongest within 48 hours after admission. The relation between sleep, sound and delirium, however, needs further research. (Crit Care. 2012 May 4;16(3):R73)

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Effect of Earplugs and Eye Mask on Nocturnal Sleep,Melatonin, and Cortisol in a Simulated Intensive Care Unit Environtment

ABSTRACT

Rong-fang Hu, Xiao-ying Jiang, Yi-ming Zeng, Xiao-yang Chen, You-hua Zhang

Introduction: Environmental stimulus, especially noise and light, is thought to disrupt sleep in patients in the intensive care unit (ICU). This study aimed to determine the physiological and psychological effects of ICU noise and light, and of earplugs and eye masks, used in these conditions in healthy subjects.

Methods: Fourteen subjects underwent polysomnography under four conditions: adaptation, baseline, exposure to recorded ICU noise and light (NL), and NL plus use of earplugs and eye masks (NLEE). Urine was analyzed for melatonin and cortisol levels. Subjects rated their perceived sleep quality, anxiety levels and perception of environmental stimuli.

Results: Subjects had poorer perceived sleep quality, more light sleep, longer rapid eye movement (REM) latency, less REM sleep when exposed to simulated ICU noise and light (P < 0.05). Nocturnal melatonin (P = 0.007) and cortisol secretion levels (P = 0.004) differed significantly by condition but anxiety levels did not (P = 0.06). Use of earplugs and eye masks resulted in more REM time, shorter REM latency, less arousal (P < 0.05) and elevated melatonin levels (P = 0.002).

Conclusions: Earplugs and eye masks promote sleep and hormone balance in healthy subjects exposed to simulated ICU noise and light, making their promotion in ICU patients reasonable. (Crit Care. 2010; 14(2): R66)

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Effect of daily sedative interruption on sleep stages of mechanically ventilated patients receiving midazolam by infusion

SUMMARY

J. OTO, K. YAMAMOTO, S. KOIKE, H. IMANAKA§, M. NISHIMURA

Daily sedative interruption (DSI) may reduce excessive sedation and shorten the duration of mechanical ventilation. It is not clear, however, how DSI affects sleep characteristics. For patients receiving mechanicalventilation, we compared the effect on sleep quality of DSI and continuous sedation (CS). Twenty-two mechanically ventilated patients who were receiving midazolam by infusion were randomly assigned to two groups, DSI (n=11) or CS (n=11). In the DSI group, sedatives were interrupted until the patients awoke and expressed discomfort, after which midazolam or opioids were administered intermittently as needed during the daytime (0600 to 2100 hours); during the night (2100 to 0600) midazolam was administered intravenouslyto maintain Ramsay sedation scale 4 to 5. In the CS group, the sedatives were titrated to obtain Ramsay sedation scale 4 to 5 throughout the day. The polysomnography of each patient was recorded continuously over a 24 hour period. Sleep stages were analysed using Rechtschaffen and Kales criteria. In the DSI group, the amount of stage 3 and 4 non-rapid eye movement sleep (slow wave sleep) was longer (6 vs 0 minutes, P=0.04) and rapid eye movement sleep was longer than in CS (54 vs 0 minutes, P=0.02). In the CS group, total sleep time during night-time was longer (8.7 vs 7.3 hours, P=0.047) and frequency of arousal was lower (2.2 vs 4.4 event/hour, P=0.03) than those in the DSI group. All mechanically ventilated patients demonstrated abnormal sleep architecture, but, compared with CS, DSI increased the amount of slow wave sleep and rapid eye movement sleep.

(Anaesth Intensive Care 2011; 39: 392-400)

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Contribution Of The Intensive Care Unit Environment To Sleep Disruption In Mechanically Ventilated Patients And Healthy Subjects

ABSTRACT

Gabor JY, Cooper AB, Crombach SA, Lee B, Kadikar N, Bettger HE, Hanly PJ.

Recent studies have challenged the traditional hypothesis that excessive environmental noise is central to the etiology of sleep disruption in the intensive care unit (ICU). We characterized potentially disruptive ICU noise stimuli and patient-care activities and determined their relative contributions to sleep disruption. Furthermore, we studied the effect of noise in isolation by placing healthy subjects in the ICU in both normal and noise-reduced locations. Seven mechanically ventilated patients and six healthy subjects were studied by continuous 24-hour polysomnography with time-synchronized environmental monitoring. Sound elevations occurred 36.5 +/- 20.1 times per hour of sleep and were responsible for 20.9 +/- 11.3% of total arousals and awakenings. Patient-care activities occurred 7.8 +/- 4.2 times per hour of sleep and were responsible for 7.1 +/- 4.4% of total arousals and awakenings. Healthy subjects slept relatively well in the typically loud ICU environment and experienced a quantitative, but not qualitative, improvement in sleep in a noise-reduced, single-patient ICU room. Our data indicate that noise and patient-care activities account for less than 30% of arousals and awakenings and suggest that other elements of the critically ill patient's environment or treatment should be investigated in the pathogenesis of ICU sleep disruption. (Am J Respir Crit Care Med. 2003 Mar 1;167(5):708-15)

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Common Sleep Problems In ICU: Heart Failure And Sleep-Disordered Breathing Syndromes

INTRODUCTION

Matthew T. Naughton, MD, FRACP

Heart failure and sleep-disordered breathing are important to the intensivist. Sleep is frequently the ‘‘stress’’ that destabilizes cardiac function and results in the symptoms that many patients develop that require admission to ICU. Sleep-related breathing disorders are intertwined with cardiovascular disease by virtue of their shared real estate (ie, the lungs) and common interacting cardiopulmonary physiology. The therapies that have been used to manage long-term obstructive sleep apnea–hypopnea syndrome (OSAHS) and hypoventilation disorders with various noninvasive ventilation (NIV) devices (bilevel positive airway pressure [PAP], continuous PAP [CPAP], volume-cycled portable devices) in the domiciliary setting have been used as the backbone in the development of comfortable, portable, and effective NIV devices that are used by intensivists and emergency physicians to manage acute cardiac and respiratory failure today. (Crit Care Clin. 2008 Jul;24(3):565-87, vii-viii. doi: 10.1016/j.ccc.2008.02.004)

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Clinical Review The Impact of Noise on Patients Sleep and The Effectiveness of Noise Reduction Strategies in Intensive Care Units

ABSTRACT

Xie H, Kang J, Mills GH.

Excessive noise is becoming a significant problem for intensive care units (ICUs). This paper first reviews the impact of noise on patients' sleep in ICUs. Five previous studies have demonstrated such impacts, whereas six other studies have shown other factors to be more important. Staff conversation and alarms are generally regarded as the most disturbing noises for patients' sleep in ICUs. Most research in this area has focused purely on noise level, but work has been very limited on the relationships between sleep quality and other acoustic parameters, including spectrum and reverberation time. Sound-absorbing treatment is a relatively effective noise reduction strategy, whereas sound masking appears to be the most effective technique for improving sleep. For future research, there should be close collaboration between medical researchers and acousticians. (Crit Care. 2009;13(2):208. doi: 10.1186/cc7154. Epub 2009 Mar 9)

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Clinical Review Sleep Measurement in Critical Care Patients: Research and Clinical Implication

ABSTRACT

Richard S Bourne, Cosetta Minelli, Gary H Mills, and Rosalind Kandler

Sleep disturbances are common in critically ill patients and have been characterised by numerous studies using polysomnography. Issues regarding patient populations, monitoring duration and timing (nocturnal versus continuous), as well as practical problems encountered in critical care studies using polysomnography are considered with regard to future interventional studies on sleep. Polysomnography is the gold standard in objectively measuring the quality and quantity of sleep. However, it is difficult to undertake, particularly in patients recovering from critical illness in an acute-care area. Therefore, other objective (actigraphy and bispectral index) and subjective (nurse or patient assessment) methods have been used in other critical care studies. Each of these techniques has its own particular advantages and disadvantages. We use data from an interventional study to compare agreement between four of these alternative techniques in the measurement of nocturnal sleep quantity. Recommendations for further developments in sleep monitoring techniques for research and clinical application are made. Also, methodological problems in studies validating various sleep measurement techniques are explored.

(Crit Care. 2007; 11(4): 226.)

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Association of Sleep Duration with Mortality from Cardiovascular Disease and Other Causes for Japanese Men and Women the JACC Study

ABSTRACT

Ikehara S, Iso H, Date C, Kikuchi S, Watanabe Y, Wada Y, Inaba Y, Tamakoshi A; JACC Study Group

STUDY OBJECTIVES: To examine sex-specific associations between sleep duration and mortality from cardiovascular disease and other causes.

DESIGN: Cohort study.

SETTING: Community-based study.

PARTICIPANTS: A total of 98,634 subjects (41,489 men and 57,145 women) aged 40 to 79 years from 1988 to 1990 and were followed until 2003.

INTERVENTIONS: N/A.

MEASUREMENTS AND RESULTS: During a median follow-up of 14.3 years, there were 1964 deaths (men and women: 1038 and 926) from stroke, 881 (508 and 373) from coronary heart disease, 4287 (2297 and 1990) from cardiovascular disease, 5465 (3432 and 2033) from cancer, and 14,540 (8548 and 5992) from all causes. Compared with a sleep duration of 7 hours, sleep duration of 4 hours or less was associated with increased mortality from coronary heart disease for women and noncardiovascular disease/noncancer and all causes in both sexes. The respective multivariable hazard ratios were 2.32 (1.19-4.50) for coronary heart disease in women, 1.49 (1.02-2.18) and 1.47 (1.01-2.15) for noncardiovascular disease/noncancer, and 1.29 (1.02-1.64) and 1.28 (1.03-1.60) for all causes in men and women, respectively. Long sleep duration of 10 hours or longer was associated with 1.5- to 2-fold increased mortality from total and ischemic stroke, total cardiovascular disease, noncardiovascular disease/noncancer, and all causes for men and women, compared with 7 hours of sleep in both sexes. There was no association between sleep duration and cancer mortality in either sex.

CONCLUSIONS: Both short and long sleep duration were associated with increased mortality from cardiovascular disease, noncardiovascular disease/noncancer, and all causes for both sexes, yielding a U-shaped relationship with total mortality with a nadir at 7 hours of sleep. (Sleep. 2009 Mar;32(3):295-301)

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Assessment of Sleep in Ventilator-Supported Critically Ill Patients

ABSTRACT

Ambrogio C; Koebnick J; Quan SF; Ranieri VM; Parthasarathy

Objectives: In critically ill patients, sleep derangements are reported to be severe using Rechtschaffen and Kales (R&K) methodology; however, whether such methodology can reliably assess sleep during critical illness is unknown. We set out to determine the reproducibility of 4 different sleep-assessment methods (3 manual and 1 computer-based) for ventilator-supported critically ill patients and also to quantify the extent to which the reproducibility of the manual methods for measuring sleep differed between critically ill and ambulatory (control) patients.

Design: Observational methodologic study.

Setting: Academic center.

Patients: Critically ill patients receiving mechanical ventilation and age-matched controls underwent polysomnography.

Interventions: None.

Measurements and Results: Reproducibility for the computer-based method (spectral analysis of electroencephalography [EEG]) was better than that for the manual methods: R&K methodology and sleep-wakefulness organization pattern (P = 0.03). In critically ill patients, the proportion of misclassifications for measurements using spectral analysis, sleep-wakefulness organization pattern, and R&K methodology were 0%, 36%, and 53%, respectively (P < 0.0001). The EEG pattern of burst suppression was not observed. Interobserver and intraobserver reliability of the manual sleep-assessment methods for critically ill patients (κ = 0.52 ± 0.23) was worse than that for control patients (κ = 0.89 ± 0.13; P = 0.03). In critically ill patients, the overall reliability of the R&K methodology was relatively low for assessing sleep (κ = 0.19), but detection of rapid eye movement sleep revealed good agreement (κ = 0.70).

Conclusions: Reproducibility for spectral analysis of EEG was better than that for the manual methods: R&K methodology and sleep-wakefulness organization pattern. For assessment of sleep in critically ill patients, the use of spectral analysis, sleep-wakefulness organization state, or rapid eye movement sleep alone may be preferred over the R&K methodology. (SLEEP 2008;31(11):1559–1568)

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Adverse Environmental Conditions in the Respiratory and Medical ICU

ABSTRACT

Meyer TJ, Eveloff SE, Bauer MS, Schwartz WA, Hill NS, Millman RP.

Sleep deprivation and fragmentation occurring in the hospital setting may have a negative impact on the respiratory system by decreasing respiratory muscle function and ventilatory response to CO2. Sleep deprivation in a patient with respiratory failure may, therefore, impair recovery and weaning from mechanical ventilation. We postulate that light, sound, and interruption levels in a weaning unit are major factors resulting in sleep disorders and possibly circadian rhythm disruption. As an initial test of this hypothesis, we sampled interruption levels and continuously monitored light and sound levels for a minimum of seven consecutive days in a medical ICU, a multiple bed respiratory care unit (RCU) room, a single-bed RCU room, and a private room. Light levels in all areas maintained a day-night rhythm, with peak levels dependent on window orientation and shading. Peak sound levels were extremely high in all areas representing values significantly higher than those recommended by the Environmental Protection Agency as acceptable for a hospital environment. The number of sound peaks greater than 80 decibels, which may result in sleep arousals, was especially high in the intensive and respiratory care areas, but did show a day-night rhythm in all settings. Patient interruptions tended to be erratic, leaving little time for condensed sleep. We conclude that the potential for environmentally induced sleep disruption is high in all areas, but especially high in the intensive and respiratory care areas where the negative consequences may be the most severe. (Chest. 1994 Apr;105(4):1211-6)

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Adverse Effects of Sleep Deprivation in the ICU

 Rachel E. Salas, MDa, Charlene E. Gamaldo, MD.

The hospital is not conducive to sleep. Patients commonly recount major issues with sleep initiation and poor sleep quality during their hospital stay. Moreover, patients in the ICU are particularly susceptible to sleep disruption secondary to environmental and medical issues. Despite the frequency of sleep disruption in the ICU, the quality of critically ill patients’ sleep is often overlooked. When questioned following discharge from the ICU, patients frequently report the occurrence of sleep disruption during their stay, suggesting that sleep disruption in the ICU is widespread. Disturbed sleep patterns result in the undesirable consequences of daytime sleepiness, lethargy, irritability, confusion, and poor short-term memory. The potential negative neurologic sequelae from sleep loss may often lead to additional tests to evaluate for change in mentation (eg, frequent neurologic checks, head CTs, or MRIs), potentially resulting not only in an increased financial burden to an already strained health care system but also in extended hospital stays. Patients requiring additional work-up because of their sleep-related change in alertness are less able to receive the care and services, such as physical and occupational therapy, that benefit timely discharges. In fact, increasing evidence supports the concept that

sleep disturbance in the ICU can affect patient mortality during hospitalization and after discharge from the unit. The level of impact of the ICU experience on a patient seems to be multifactorial; hence, this article discusses the following issues essential to understanding the factors associated with sleep loss in the ICU: (1) core elements to consider from the baseline sleep history, (2) impact of the ICU environment on the ICU patient’s sleep pattern, and (3) overall systematic impact of sleep deprivation on the ICU patient. (Crit Care Clin 24 (2008) 461–476)

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Actigraphy in the Critically Ill: Correlation With Activity, Agitation, and Sedation

ABSTRACT

By Mary Jo Grap, RN, PhD, ACNP, C. Todd Borchers, RN, MS, Cindy L. Munro, RN, PhD, ANP, R. K. Elswick, Jr, PhD, and Curtis N. Sessler, MD.

OBJECTIVES To determine the feasibility of continuous measurement of limb movement via wrist and ankle actigraphy (an activity measure) in critically ill patients and to compare actigraphy measurements with observed activity, subjective scores on sedation-agitation scales, and heart rate and blood pressure of patients.

METHODS In a prospective, descriptive, correlational study, all activity of 20 adult patients in medical and coronary care units in a university medical center were observed for 2 hours and documented. Wrist and ankle actigraphy, heart rate, and systolic and diastolic blood pressure data were collected every minute. The Comfort Scale and the Richmond Agitation-Sedation Scale were completed at the beginning of the observation period and 1 and 2 hours later.

RESULTS Wrist actigraphy data correlated with scores on the Richmond Agitation-Sedation Scale (r=0.58) and the Comfort Scale (r=0.62) and with observed stimulation and activity events of patients (r = 0.45). Correlations with systolic, diastolic, and mean arterial pressures were weaker. Wrist and ankle actigraphy data were significantly correlated (r = 0.69; P < .001); however, their mean values (wrist, 418; ankle, 147) were significantly different (t=5.77; P<.001).

CONCLUSIONS Actigraphy provides a continuous recording of patients’ limb movement. Actigraphy measurements correlate well with patients’ observed activity and with subjective scores on agitation and sedation scales. Actigraphy may become particularly important as a continuous measurement of activity for use in behavioral research and may enhance early recognition and management of the excessive activity that characterizes agitation. (American Journal of Critical Care. 2005;14:52-60)

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Abnormal Sleep Wake Cycles and the Effect of Environtmental Noise on Sleep Disruption in the Intensive Care Unit

ABSTRACT

Neil S. Freedman, Joost Gazendam, Lachelle Levan, Allan I. Pack, And Richard J. Schwab

Little is known about sleep/wake abnormalities in intensive care and less is known about the mechanisms responsible for these abnormalities. We studied 22 (20 mechanically ventilated) medical intensive care unit (ICU) patients with continuous polysomnography (PSG) and environmental noise measurements for 24–48 h to characterize sleep–wake patterns and objectively determine the effect of environmental noise on sleep disruption. All 22 patients demonstrated sleep–wake cycle abnormalities. There were large variations in total sleep time (TST) with the mean total sleep time per 24-h study period of 8.8±5.0 h. Sleep–wake cycles were fragmented and nonconsolidated with a mean of 57±18% and 43±18% of the TST occurring during the day and night, respectively. Environmental noise was responsible for 11.5 and 17% of theoverall arousals and awakenings from sleep, respectively. The mean noise arousal index was 1.9±2.1 arousals/h sleep. Conclusions:(1) ICU patients are qualitatively, but not necessarily quantitatively, sleep deprived; and (2) although environmental noise is in part responsible for sleep–wake abnormalities, it is not responsible for the majority of the sleep fragmentation and may therefore not be as disruptive to sleep as the previous literature suggests. (Am J Respir Crit Care Med Vol 163. pp 451–457, 2001)

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Treatment of Hyperglycemia in Critically Ill Patients: Comparison of Different Glucose Management Protocols

ABSTRACT

Blaha J, Kremen J, Anderlova K, Svacina S, Kunstyr J and Haluzik M

Increased blood glucose levels frequently occur in critically ill patients both with and without previous presence of diabetes. Numerous studies have shown that its normalization by intensive insulin treatment markedly improve the outcome of critically ill patients. Several glucose management protocols have been developed and showed different effectiveness in normalizing blood glucose. Here we describe 3 glucose management protocols from 3 different European cardiosurgical centers: General University Hospital in Prague, Medical University in Graz, Royal Brompton Hospital in London and compare them with the glucose management protocol from “Leuven study”. We further tested the effectiveness of these protocols in 10 randomly selected patients from each center. We show that continuous insulin infusion is a necessary prerequisite for satisfactory blood glucose control in critically ill patients both with and without previous history of insulin-treated diabetes. Implementation of iv insulin boluses in combination with continuous insulin infusion did not further improve glucose control in this study.

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Role of Intravenous Insulin Therapy In Critically Ill Patients

ABSTRACT

Greet H. Van den Berghe, MD, PhD

Objective: To summarize the novel evidence for maintaining normoglycemia with intensive insulin therapy during intensive care in critically ill patients, with or without diabetes, in the surgical intensive-care unit.

Results: Although the association between hyperglycemia and adverse outcomes of trauma or surgical procedures necessitating intensive care was known, only one intervention study has investigated the causality of this association. This study showed that tight blood glucose control with insulin, aiming for strict normoglycemia (80 to 110 mg/dL or 4.5 to 6.1 mmol/L) during intensive care, dramatically decreased morbidity and mortality. The clinical benefits were present whether or not patients had previously diagnosed diabetes, and they seemed independent of severity and type of critical illness. Multivariate logistic regression analysis indicated that metabolic control, rather than insulin dose per se, statistically explains the beneficial effects of intensive insulin therapy on outcomes of critical illness. Other metabolic effects besides blood glucose control, however, such as normalization of dyslipidemia, and immunologic effects, such as suppression of excessive inflammation and improvement of macrophage function, accompany glycemic control in critically ill patients. These effects seem to surpass the level of glycemic control in explaining the clinical benefits of intensive insulin therapy on sepsis, organ failure, and death. Ongoing studies are attempting to clarify the mechanisms that underlie the beneficial effects of this simple and cost-saving intervention.

Conclusion: The available evidence favors targeting normoglycemia (blood glucose levels of less than 110 mg/dL or 6.1 mmol/L) by insulin infusion in all adult surgical

intensive-care patients. Whether these findings are applicable to nonsurgical intensive-care or to pediatric patients in the intensive care unit remains unclear.

(Endocr Pract. 2004;10[Suppl 2]:17-20)

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intensive insulin therapy in Critically Ill Patients

ABSTRACT

GREET VAN DEN BERGHE, M.D., PH.D., et al.

Background Hyperglycemia and insulin resistance are common in critically ill patients, even if they have not previously had diabetes. Whether the normalization

of blood glucose levels with insulin therapy improves the prognosis for such patients is not known.

Methods We performed a prospective, randomized, controlled study involving adults admitted to our surgical intensive care unit who were receiving mechanical

ventilation. On admission, patients were randomly assigned to receive intensive insulin therapy (maintenance of blood glucose at a level between 80 and

110 mg per deciliter) or conventional treatment (infusion of insulin only if the blood glucose level exceeded 215 mg per deciliter and maintenance of glucose at a level between 180 and 200 mg per deciliter).

Results At 12 months, with a total of 1548 patients enrolled, intensive insulin therapy reduced mortality during intensive care from 8.0 percent with conventional

treatment to 4.6 percent (P<0.04, with adjustment for sequential analyses). The benefit of intensive insulin therapy was attributable to its effect on mortality among patients who remained in the intensive care unit for more than five days (20.2 percent with conventional treatment, as compared with 10.6 percent with intensive insulin therapy; P=0.005). The greatest reduction in mortality involved deaths due to

multiple-organ failure with a proven septic focus. Intensive insulin therapy also reduced overall in-hospital mortality by 34 percent, bloodstream infections by 46 percent, acute renal failure requiring dialysis or hemofiltrationby 41 percent, the median number of red-cell transfusions by 50 percent, and critical-illness polyneuropathy by 44 percent, and patients receiving intensive therapy were less likely to require prolonged mechanical ventilation and intensive care.

Conclusions Intensive insulin therapy to maintain blood glucose at or below 110 mg per deciliter reduces morbidity and mortality among critically ill patients

in the surgical intensive care unit. (N Engl J Med 2001;345:1359-67.)

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Intensive Insulin Therapy in Critically Ill Hospitalized Patients: Making it Safe and Effective

ABSTRACT

David C. Klonoff, M.D., FACP

Intensive insulin therapy (IIT) for hyperglycemia in critically ill patients has become a standard practice. Target levels for glycemia have fluctuated since 2000, as evidence initially indicated that tight glycemic control to so-called normoglycemia (80–110 mg/dl) leads to the lowest morbidity and mortality without hypoglycemic

complications. Subsequent studies have demonstrated minimal clinical benefit combined with greater hypoglycemic morbidity and mortality with tight glycemic control in this population. The consensus glycemic targets were then liberalized to the mid 100s (mg/dl).

Handheld POC blood glucose (BG) monitors have migrated from the outpatient setting to the hospital environment because they save time and money for managing critically ill patients who require IIT. These devices are less accurate than hospital-grade POC blood analyzers or central laboratory analyzers.

Three questions must be answered to understand the role of IIT for defined populations of critically ill patients: (1) How safe is IIT, with various glycemic targets, from the risk of hypoglycemia? (2) How tightly must BG be controlled for this approach to be effective? (3) What role does the accuracy of BG measurements play in affecting the safety of this method? For each state of impaired glucose regulation seen in the hospital, such as hyperglycemia, hypoglycemia, or glucose variability, the benefits, risks, and goals of treatment, including IIT, might differ.

With improved accuracy of BG monitors, IIT might be rendered even more intensive than at present, because patients will be less likely to receive inadvertent overdosages of insulin. Greater doses of insulin, but with dosing based on more accurate glucose levels, might result in less hypoglycemia, less hyperglycemia, and less glycemic variability. (J Diabetes Sci Technol 2011;5(3):755-767)

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Intensive Insulin Therapy for The Treatment of Hyperglycemia in Critically Ill Adults: A Qualitative Systematic Review and Critical Appraisal of the Evidence

ABSTRACT

Rattan Juneja MD; Michael E. Stuart, MD; Sheri A. Strite

Background: Hyperglycemia in intensive care patients is associated with high mortality, but optimal management of this population with insulin therapy is Methods: We utilized the extensive search from a recent published meta-analysis and conducted an updated search using MEDLINE (2008-2009), the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. We assessed bias of trials using a detailed checklist to document the overall quality of the evidence for mortality and hypoglycemia in intensive care populations.

Findings: We included a total of 17 clinical trials totaling 12,345 patients. All included trials were rated as being at medium risk of bias. We identified eight groups of patients in which intensive insulin treatment has been compared to less intensive insulin therapy. Mortality rates varied by patient population with rates of < 16% in predominantly surgical patients with mixed conditions to nearly 75% in neurosurgical patients. Overall, mortality rates ranged from 4% to 74% but the overall level of evidence for mortality was inconclusive. Hypoglycemia rates ranged from 0% to 94% and the overall level of evidence for hypoglycemia was borderline.

Interpretation: The evidence is insufficient for determining the effect of intensive

insulin treatment compared to less intensive treatment in acutely ill hyperglycemic

patients. The evidence does not justify guideline recommendations for specific glycemic target ranges for adults being treated in intensive care units. Further research is needed, but should be carefully planned with attention to trial bias, populations, type of insulin protocols used, adherence, co-interventions, and frequency of blood glucose testing to avoid the heterogeneity and bias present in currently available research.

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Intensive Insulin Therapy and Mortality in Critically Ill Patients

ABSTRACT

Miriam M Treggiari, Veena Karir, N David Yanez, Noel S Weiss, Stephen Daniel and Steven A Deem

Introduction Intensive insulin therapy (IIT) with tight glycemic control may reduce mortality and morbidity in critically ill patients and has been widely adopted in practice throughout the world. However, there is only one randomized controlled trial showing unequivocal benefit to this approach and that study population was dominated by post-cardiac surgery patients. We aimed to determine the association between IIT and mortality in a mixed population of critically ill patients.

Methods We conducted a cohort study comparing three consecutive time periods before and after IIT protocol implementation in a Level 1 trauma center: period I (no

protocol); period II, target glucose 80 to 130 mg/dL; and period III, target glucose 80 to 110 mg/dL. Subjects were 10,456 patients admitted to intensive care units (ICUs) between 1 March 2001 and 28 February 2005. The main study endpoints

were ICU and hospital mortality, Sequential Organ Failure Assessment score, and occurrence of hypoglycemia. Multivariable regression analysis was used to evaluate mortality and organ dysfunction during periods II and III relative to period I.

Results Insulin administration increased over time (9% period I, 25% period II, and 42% period III). Nonetheless, patients in period III had a tendency toward higher adjusted hospital mortality (odds ratio [OR] 1.15, 95% confidence interval [CI] 0.98, 1.35) than patients in period I. Excess hospital mortality in period III was present primarily in patients with an ICU length of stay of 3 days or less (OR 1.47, 95% CI 1.11, 1.93 There was an approximately fourfold increase in the incidence of hypoglycemia from periods I to III.

Conclusion A policy of IIT in a group of ICUs from a single institution was not associated with a decrease in hospital mortality. These results, combined with the findings from several recent randomized trials, suggest that further study is needed

prior to widespread implementation of IIT in critically ill patients.

Critical Care 2008, 12:R29 (doi:10.1186/cc6807)

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Insulin Therapy for Critical Ill Hospitalized Patients

ABSTRACT

Anastassios G. Pittas, MD; Richard D. Siegel, MD; Joseph Lau, MD

Background: Hyperglycemia is common in critically ill hospitalized patients, and it is associated with adverse outcomes, including increased mortality. The objective of

this meta-analysis was to determine the effect of insulin therapy initiated during hospitalization on mortality in adult patients with a critical illness.

Methods: An electronic search in the Englishlanguage articles of MEDLINE and the Cochrane Controlled Clinical Trials Register and a hand search of key journals and relevant review articles were performed. Randomized controlled trials that reported mortality data on critically ill hospitalized adult patients who were treated

with insulin were selected. Data on patient demographics, hospital setting, intervention (formulation and dosage of insulin, delivery method, and duration of therapy), mortality outcomes, adverse events, and methodological quality were extracted.

Results: Thirty-five trials met the inclusion criteria. Combining data from all trials using a random-effects model showed that insulin therapy decreases short-term mortality by 15% (relative risk [RR], 0.85; 95% confidence interval [CI], 0.75-0.97). In subgroup analyses, insulin therapy decreased mortality in the surgical intensive care unit (RR, 0.58; 95% CI, 0.22-0.62), when the aim of therapy was glucose control (RR, 0.71; 95% CI, 0.54-0.93), and in patients with diabetes mellitus (RR, 0.73; 95% CI, 0.58-0.90). A near-significant trend toward decreasing mortality was seen in patients with acute myocardial infarction who did not receive reperfusion therapy (RR, 0.84; 95% CI, 0.71-1.00). No randomized trials of insulin in the medical intensive care unit were identified.

Conclusion: Insulin therapy initiated in the hospital in critically ill patients has a beneficial effect on shortterm mortality in different clinical settings.

(Arch Intern Med. 2004;164:2005-2011)

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Improvement of Glucose Control in The Intensive Care Unit (An Interdisciplinary Collaboration Study)

ABSTRACT

By Ulrike Holzinger, MD, Monika Feldbacher, RN, Adelbert Bachlechner, RN, Reinhard Kitzberger, MD, Valentin Fuhrmann, MD, and Christian Madl, MD

Background Strict glycemic control in critically ill patients is challenging for both physicians and nurses.

Objectives To determine the effect of focused education of intensive care staff followed by implementation of a glucose control protocol.

Methods A prospective observational study in a medical intensive care unit in a university hospital. After intensive education of nurses and physicians, a glucose control protocol with a nurse-managed insulin therapy algorithm was developed and implemented. Every measured blood glucose value and insulin dose per hour and per day were documented in 36 patients before and 44 patients after implementation of

the protocol.

Results Median blood glucose levels decreased after implementation of the protocol (133 vs 110 mg/dL; P < .001). The amounts of time when patients’ blood glucose levels were less than 110 mg/dL and less than 150 mg/dL increased after implementation of the protocol (8% vs 44%; 75% vs 96%; P<.001). The median use of insulin increased after implementation of the protocol (28 vs 35 IU/day; P=.002). Diabetic patients had higher median blood glucose levels than did nondiabetic patients both before (138 vs 131 mg/dL) and after (115 vs 108 mg/dL; P<.001) implementation, although median insulin use also increased (before implementation, 33 vs 26 IU/day; P=.04; after implementation, 46 vs 30 IU/day; P < .001).

Conclusions Use of a collaboratively developed glucose control protocol led to decreased median blood glucose levels and to longer periods of normoglycemia. Despite increased insulin use, glucose control was worse in diabetic patients.

(American Journal of Critical Care. 2008;17:150-158)

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Hypoglycemic Events in Intesive Care Patients: Analysis by Insulin Administration Method and Sample Type

ABSTRACT

By Marta Raurell Torredà, RN, MSN, Emilia Chirveches Pérez, RN, MSN, Maite Domingo Aragón, RN, Rosa Martínez Ribe, RN, Emma Puigoriol Juvanteny, MStat, and Quintí Foguet Boreu, MD, PhD

Background Intensive insulin treatment is associated with an increased risk of hypoglycemia, so strict glycemic monitoring is essential. The best type of sample for identifying hypoglycemia remains under debate.

Objectives To establish the number of hypoglycemic events in intensive care patients relative to insulin administration method and the method used to collect the blood sample.

Methods Retrospective descriptive study lasting 6 months. Hypoglycemia was defined as a blood glucose level less than 80 mg/dL (mild: 50-79 mg/dL, severe: <50 mg/dL), measured with a bedside glucometer and blood from the arterial catheter

or fingerstick, in critically ill patients who require insulin administered subcutaneously (with sliding scales) or via continuous intravenous perfusion (intense infusion protocol with a nurse-managed insulin therapy algorithm).

Results Analysis of the 6636 samples from 144 critically ill patients revealed 188 mildly hypoglycemic samples (2.8%) and 3 severely hypoglycemic samples (0.04%). The prevalence of mild hypoglycemia was greater when insulin was administered

intravenously (3.2%) rather than subcutaneously (2.3%; P = .04). Among patients receiving insulin intravenously, hypoglycemia was found more often in arterial (4.5%) than in capillary (2.8%) blood (P = .01). The prevalence of hypoglycemia in capillary blood samples did not differ significantly between subcutaneous (2.3%) and intravenous (2.8%) insulin therapies (P = .21).

Conclusions With a target blood glucose level of 110 to 140 mg/dL, few hypoglycemic events are detected in critically ill patients, regardless of whether insulin is administered intravenously or subcutaneously. Analysis of solely arterial samples may yield a higher prevalence of hypoglycemia than otherwise.

(American Journal of Critical Care. 2011;20:e115-e121)

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Hyperglycemia related Mortality in Critically Ill Patients Varies with Admission Diagnosis

ABSTRACT

Mercedes Falciglia, MD; Ron W. Freyberg, MS; Peter L. Almenoff, MD; David A. D’Alessio, MD; Marta L. Render, MD

Objectives: Hyperglycemia during critical illness is common and is associated with increased mortality. Intensive insulin therapy has improved outcomes in some, but not all, intervention trials. It is unclear whether the benefits of treatment differ among specific patient populations. The purpose of the study was to determine the association between hyperglycemia and risk–adjusted mortality in critically ill patients and in separate groups stratified by admission diagnosis. A secondary purpose was to determine whether mortality risk from hyperglycemia varies with

intensive care unit type, length of stay, or diagnosed diabetes. Design: Retrospective cohort study.

Setting: 173 U.S. medical, surgical, and cardiac intensive care units.

Patients: 259,040 admissions from October 2002 to September 2005; unadjusted mortality rate, 11.2%.

Interventions: None.

Measurements and Main Results: A two–level logistic regression model determined the relationship between glycemia and mortality. Age, diagnosis, comorbidities, and laboratory variables were used to calculate a predicted mortality rate, which was then

analyzed with mean glucose to determine the association of hyperglycemia with hospital mortality. Hyperglycemia was associated with increased mortality independent of illness severity. Compared with normoglycemic individuals (70–110 mg/dL), adjusted odds of mortality (odds ratio, [95% confidence interval]) for mean glucose 111–145, 146–199, 200–300, and >300 mg/dL was 1.31(1.26 –1.36), 1.82(1.74 –1.90), 2.13(2.03–2.25), and 2.85(2.58–3.14), respectively. Furthermore, the adjusted odds of mortality related to hyperglycemia varied with admission diagnosis, demonstrating a clear association in some patients (acute myocardial infarction, arrhythmia, unstable angina, pulmonary embolism) and little or no association in others. Hyperglycemia was associated with increased mortality independent of intensive care unit type, length of stay, and diabetes.

Conclusions: The association between hyperglycemia and mortality implicates hyperglycemia as a potentially harmful and correctable abnormality in critically ill patients. The finding that hyperglycemia–related risk varied with admission diagnosis suggests differences in the interaction between specific medical conditions and injury from hyperglycemia. The design and interpretation of future trials should consider the primary disease states of patients and the balance of medical conditions in the intensive care unit studied. (Crit Care Med 2009; 37:000–000).

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