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*New* Literature Monitor: Selected Content from March 2010

DO SEDATION PROTOCOLS FOR VENTILATED PATIENTS NEED REVISION?

Critically ill patients who received mechanical ventilation without sedation had significantly fewer days on the ventilator than those who received interrupted sedation, according to a study in the February 6 Lancet.

Thomas Strøm, MD, of the University of Southern Denmark, and colleagues tracked ventilated patients who either received no sedation with IV analgesics (intervention group; n = 55) or who were sedated with 20 mg/mL propofol for 48 hours and 1 mg/mL midazolam thereafter with daily interruption until awake (control group; n = 58). Both groups received bolus doses of 2.5 or 5.0 mg morphine as needed.

On the primary outcome of the number of days without mechanical ventilation in a 28-day period, the intervention group had an average of 13.8 ventilator-free days, compared with 9.6 days in the control group. The intervention group also spent fewer days in the ICU by a difference of 9.7 days and spent an average of 24 fewer days in the hospital. The researchers found no between-group differences in the number of accidental extubations, the need for CT or MRI brain scans, or the incidence of ventilator-associated pneumonia. The intervention group had a greater frequency of agitated delirium.

Continuous sedation is the standard treatment for critically ill patients on mechanical ventilation and previous studies have shown a beneficial effect of daily interruption of sedation; however, no sedation of these patients is the standard protocol at the study hospital, the researchers noted. “Our study responded to calls in editorials and review articles for randomized trials aiming to reduce routine use of sedation,” they said. “Results from this single-center study suggest that a strategy of no sedation is promising, but a multicenter trial is needed to show that the benefits of this strategy can be reproduced in other facilities.”

The appropriate amount of sedation in the ICU has become a “major issue” regarding mechanical ventilation, Laurent Brochard, MD, noted in an accompanying editorial. “To avoid misuse [of sedation], this practice should be repeatedly reviewed for every patient from at least four standpoints.” He recommended physicians ask the following questions in analyzing patients: Is sedation and analgesic drugs needed from the start? Does the patient have comorbidities that result in drug accumulation? Could a different ventilator setting reduce the need for drug treatment? Once sedated, does the patient need to continue with sedation?

The benefits of no sedation—shorter length of stays in ICU and hospital—need to be weighed against the negatives, said Brochard, of the Assistance Publique-Hôpitaux de Paris, the Institut National de la Santé et de la Recherche Médicale, and the Université Paris-Est. In the current study, the increased rate of delirium in nonsedated patients required “an extra person … at the bedside to comfort and reassure patients more often in the intervention group than the control group (20% vs 5%) for two to three days,” he pointed out. “Long-term follow-up of these patients will be important to assess the occurrence of post-traumatic stress disorder or painful recollections.” 

Brochard L. Less sedation in intesive care—the pendulum swings back. Lancet. 2010;375(9713):436-438.
Strøm T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet. 2010;375(9713):475-480.

News Roundup: Selected Content from February 2010

Disinfectant use can cause bacteria to become resistant to both antibiotics and disinfectants, according to a study in the January Microbiology. Researchers investigated the link between bacterial adaptation to biocides and antibiotics by introducing small amounts of benzalkonium chloride (BKC) into a continuous culture of Pseudomonas aeruginosa, and found that when nonlethal amounts of disinfectant were added to the bacteria culture, the adapted bacteria were more likely to survive. “In principle this means that residue from incorrectly diluted disinfectants left on hospital surfaces could promote the growth of antibiotic-resistant bacteria,” according to the lead study author. “What is more worrying is that bacteria seem to be able to adapt to resist antibiotics without even being exposed to them.”

Exposure to childhood trauma may be associated with an increased risk of lung cancer and premature death from the disease, according to a study published January 19 in the online journal BMC Public Health. Between 1995 and 1997, investigators surveyed 17,337 adults regarding health behaviors, health status, and exposure to adverse childhood experiences (ACEs), defined as physical, emotional, or sexual abuse; domestic violence; parental divorce; or living with family members who were mentally ill, substance abusers, or sent to prison. Upon follow-up in 2005, researchers found subjects with ACE scores of 6 or more were nearly 13 years younger at diagnosis than those without ACEs. “After a priori consideration of a causal pathway—ACEs lead to smoking, which leads to lung cancer—risk ratios were attenuated toward the null, although not completely,” study authors reported. “The increase in risk may only be partly explained by smoking, suggesting other possible mechanisms by which ACEs may contribute to the occurrence of lung cancer."

The Surviving Sepsis Campaign was associated with ongoing quality improvements in sepsis care and a reduction in mortality rates, as reported in an article published simultaneously in the February issues of Critical Care Medicine and Intensive Care Medicine. In a two-year, international analysis of 15,022 patients at 165 sites, researchers used a multifaceted intervention to facilitate compliance with selected guideline recommendations. Elements of the guidelines were bundled into two sets of targets—resuscitation and management—to be completed within six and 24 hours. Compliance with the entire resuscitation bundle increased from 10.9% at the end of the first quarter to 31.3% by the end of the study. Compliance with the entire management bundle started at 18.4% in the first quarter and increased to 36.1% by the end of the study. Unadjusted hospital mortality decreased from 37.0% to 30.8% over the two-year period.

News Roundup: Selected Content from January 2010

Pistachios may reduce lung cancer risk, investigators suggested. At the 2009 Cancer Prevention Research Conference, investigators randomized 36 healthy participants to eat 68 g of pistachios daily or to continue their usual diet for four weeks. A significant increase in energy-adjusted dietary intake of γ-tocopherol was observed after at weeks 3 and 4 in the intervention group, compared with the control group. In addition, investigators found a significantly higher level of serum-adjusted γ-tocopherol at the end of the intervention period in participants on the pistachio diet, compared with participants on their usual diet. “Pistachios are one of those ‘good-for-you’ nuts, and two ounces per day could be incorporated into dietary strategies designed to reduce the risk of lung cancer without significant changes in BMI,” they said.

Abstinent ecstasy users may be at an increased risk of obstructive sleep apnea (OSA), researchers observed. As reported in the December 2009 Neurology, investigators evaluated the rate of apneas, hypopneas, and apnea hypopnea indices in 71 medically healthy methylenedioxymethamphetamine (MDMA) users and 62 control participants, and found that MDMA users who had been drug free for at least two weeks had a significantly increased rate of OSA and hypopnea. The odds ratio for sleep apnea in MDMA users during non-REM sleep was 8.5; this was greater than that for obesity (6.9), investigators observed. OSA severity was significantly associated with lifetime MDMA exposure. According to the study authors, these data “lend support to the notion that brain serotonin neuronal dysfunction plays a role in the pathophysiology of sleep apnea.”

The survival rate of patients with cystic fibrosis is similar whether they undergo single or bilateral lung transplantation. In the December 1, 2009, Annals of Internal Medicine, investigators reported assessing survival times and causes of death after lung transplantation in 2,146 and 1,181 patients who underwent single and bilateral lung transplantation, respectively, from the United Network of Organ Sharing registry. Although median survival was longer after bilateral lung transplant (5.2 years), compared with a single lung transplant (3.8 years), the survival rate was similar after adjustment for baseline differences. “Single-lung transplantation confers short-term survival benefit but long-term harm, whereas bilateral transplantation confers short-term harm but long-term benefit,” the researchers concluded.

News Roundup: Selected Content from December 2009

Difficult-to-treat asthma may be a result of patients’ poor adherence to medications, researchers suggested. They compared the initial prescriptions for inhaled combination therapy and short-acting β-agonists with six-months’ worth of prescription refill records for 182 patients with severe refractory asthma. Blood plasma prednisolone and cortisol levels also were measured to determine adherence. As reported in the November 1 American Journal of Respiratory and Critical Care Medicine, more than a third of patients filled 50% or fewer inhaled medication prescriptions and 45% of patients were nonadherent to prescribed oral steroids. Since subjective measures may not be enough, “objective surrogate and direct measures of adherence should be performed as part of a difficult asthma assessment and are important before prescribing expensive novel biological therapies,” the researchers said.

Statins appear to reduce cancer risks in COPD patients, according to findings published in the November Thorax. Researchers examined data for 3,371 patients with peripheral arterial disease (1,310 of whom had COPD) and who had undergone vascular surgery between 1990 and 2006. Patients were followed for a median of five years. COPD, particularly moderate and severe disease, was associated with an increased risk of both lung cancer mortality and extrapulmonary cancer mortality (hazard ratios [HRs], 2.06 and 1.43, respectively). However, among COPD patients on statins, there was a trend toward a lower risk of total cancer mortality, compared with among COPD patients not on statins (HR, 0.57). There was a significantly decreased risk of extrapulmonary cancer mortality in COPD patients who used statins (HR, 0.49).

Of four severe sepsis treatments, administration of broad-spectrum antibiotics within one hour (versus no treatment with the first six hours of diagnosis) and administration of drotrecogin alfa (activated) was associated with reduced hospital mortality risk (odds ratios, 0.67 and 0.59, respectively), researchers asserted. Included in the final analysis of the prospective observation study were 2,796 patients with severe sepsis from 77 ICUs. As reported in the November 1 American Journal of Respiratory and Critical Care Medicine, 41.6% of these patients died before hospital discharge. Fluid challenge in the event of hypotension and/or lactate greater than 36 mg/dL, and low-dose steroid for septic shock did not appear to confer any benefits.

Literature Monitor: Selected Content from November 2009

SMOKING CESSATION DRUG MAY NOT BE RESPONSIBLE FOR SUICIDAL BEHAVIOR

An examination of data for more than 80,000 patients assigned to one of three quit-smoking regimens showed “no clear evidence” that varenicline is associated with an increased risk of fatal or nonfatal self harm, despite previous reports linking the drug to depression and suicidal thoughts. The study, published online ahead of print October 1 by BMJ, involved patients listed in the UK General Practice Research Database (GPRD) who received prescriptions for varenicline, bupropion, or nicotine replacement therapy between September 2006 and May 2008.

David Gunnell, PhD, Professor of Epidemiology in the Department of Social Medicine at the University of Bristol, UK, and colleagues used GPRD diagnostic codes to determine associations between smoking cessation products and fatal and nonfatal self harm, suicidal thoughts, depression, and all-cause mortality. Over the follow-up period, 166 episodes of nonfatal self harm, two suicides, and 37 episodes of suicidal thoughts were reported. The incidence of self harm per 100,000 person years, standardized for age and sex, was 533.1 in patients prescribed varenicline, 498.7 for patients prescribed bupropion and 751.7 for patients prescribed nicotine replacement products. Patients taking nicotine replacement therapy also had the highest rates of depression and suicidal thoughts. However, after controlling for confounding factors, the researchers found “very weak evidence” of an increased risk of self harm in relation to both varenicline (hazard ratio [HR], 1.12) and bupropion (HR, 1.17), compared with nicotine replacement therapy.

“Many prospective studies have found that smokers are at two to three times greater risk of suicide than nonsmokers. Possible explanations for this … include (a) smoking may be used as ‘self medication’ by people with mental illness, and such people are at increased risk of suicide; (b) confounding by factors such as low socioeconomic position, alcohol misuse, and psychiatric illness, all of which are associated with increased smoking prevalence and suicide risk; and (c) smoking may cause psychological illness and physical health problems, both of which are associated with suicide risk,” the study authors wrote. Additionally, since smoking is addictive, quitting smoking can cause unpleasant withdrawal symptoms, putting patients at a higher risk of self-harm, they contended.

Gunnell D, Irvine D, Wise L, et al. Varenicline and suicidal behaviour: a cohort study based on data from the General Practice Research Database. BMJ. 2009 Oct 1; [Epub ahead of print].

Literature Monitor: Selected Content from October 2009

COPD MAY BE A GREATER RISK FOR CVD THAN SMOKING

COPD is an independent risk factor for cardiovascular disease (CVD)—more than doubling the risk of heart disease, compared with no COPD—researchers reported in the September International Journal of COPD. COPD patients also are at greater risk for coronary heart disease, angina, myocardial infarction, stroke, congestive heart failure, poor circulation in lower extremities, and arrhythmia. Furthermore, study results revealed, COPD appears to be a greater risk factor for CVD than smoking.

Joseph Finkelstein, MD, PhD, of the Welch Center for Prevention Epidemiology and Clinical Research at Johns Hopkins University, Baltimore, and colleagues examined data from the 2002 National Health Interview Survey (NHIS) and analyzed 18,342 subjects ages 40 and older for associations between COPD and CVD.

Through patient self report, the investigators determined that about 5% of the subjects had COPD and 28% had CVD. With an odds ratio of 2.7, patients with COPD were more likely to have CVD (56%) than subjects without COPD (26%).

Since smoking is a risk factor common to both CVD and COPD, the researchers performed a matched case-control study from the NHIS 2002 data limited to smokers (ie, those who smoked more than 100 cigarettes in their lifetime). They found that 71% of smokers with COPD also had CVD versus only 47% of smokers without COPD. After adjustment for sociodemographic factors, health behaviors, and comorbidities, COPD was independently and positively associated with CVD; smokers with COPD had a 2.5-fold higher risk of CVD than smokers without COPD. Lower family income, drinking, and comorbidities, such as diabetes, hypertension, and high cholesterol, were significantly related to the increased risk of CVD in patients with COPD. Additionally, exercise and higher education were associated with lower risk of CVD, compared with patients who never exercise and had less than 12 years of education.

“The notion that COPD itself is an independent risk for CVD has potentially important implications,” Dr. Finkelstein and colleagues pointed out. “As a systemic inflammatory disease, COPD may accelerate the development of CVD above and beyond that due to smoking. Indeed, if the risk were great enough, therapy directed at reducing cardiovascular risk might be indicated in COPD patients, even without evidence of concomitant CVD, or the presence of other known risk factors aside from smoking.

“The results of this study are critical given the facts known about the pathogenesis of COPD and CVD and the increased prevalence of both disease processes within the general population,” the researchers concluded. Their findings, which corroborate the results of previous studies, highlight the importance of performing thorough medical examinations to assess the need for CVD treatment in COPD patients, they added.

Finkelstein J, Cha E, Scharf SM. Chronic obstructive pulmonary disease as an independent risk factor for cardiovascular morbidity. Int J Chron Obstruct Pulmon Dis. 2009;4:337-349.

News Roundup: Selected Content from September 2009

Women with asthma may experience changes in airflow and gas transfer throughout the course of their menstrual cycle, suggested researchers in the August 15 American Journal of Respiratory and Critical Care Medicine. In a study of 13 women with asthma and 10 healthy women (controls), investigators assessed spirometry, gas transfer, nitric oxide, hemoglobin, factors affecting hemoglobin binding affinity, and proangiogenic factors on a weekly basis. Airflow and lung diffusion varied the most during menses and the least early in the luteal phase, the researchers found. In asthma patients, changes in lung diffusing capacity were associated with changes in membrane diffusing capacity, but not with proangiogenic factors.

In patients with α₁-antitrypsin deficiency, outdoor air pollution may be associated with disease severity, investigators reported. In 304 patients with the PiZZ phenotype, investigators performed full lung function testing and quantitative high-resolution CT, and matched the location of patients’ houses to mean annual air pollutant data for 2006. Using regression models, they estimated that higher ozone exposure was associated with worsening in gas transfer and more severe emphysema. In addition, they found that significant associations with other pollutants was due to the collinearity with ozone. “Higher exposures to ozone may be associated with worse respiratory status in α₁-antitrypsin deficiency, identifying a group susceptible to ambient air pollution,” the study authors concluded in the August European Respiratory Journal.

Obstructive sleep apnea syndrome (OSAS) is common in patients with Down syndrome (DS), research findings suggested. In 16 adults with DS, investigators observed that 94% had abnormal polysomnograms and 63% had an Epworth sleepiness scale score of more than 10. In addition, the apnea-hypopnea index and nadir saturation were significantly worse in DS patients, compared with a retrospective sample of non-DS patients referred for clinically suspected OSAS. “We speculate that the complications of untreated OSAS (cardiovascular disease … and neurobehavioral morbidities including daytime sleepiness and impaired cognitive function) commonly overlap with the manifestations of DS and therefore may not elicit a prompt investigation in these patients,” the study authors suggested in the August 15 Journal of Clinical Sleep Medicine.

News Roundup: Selected Content from August 2009

The effect of traffic-related air pollution on childhood asthma may be increased by parental stress and in utero tobacco smoke, according to researchers. In a prospective cohort study published July 20 online ahead of print by the Proceedings of the National Academy of Sciences, investigators assessed 2,497 children ages six to nine with no history of asthma or wheeze who participated in the Children’s Health Study. Traffic-related pollution asthma risk was significantly higher in children from households with high parental stress (hazard ratio, 1.51), compared with children from households with low parental stress. “These results suggest that children from stressful households are more susceptible to the effects of traffic-related pollution and in utero tobacco smoke on the development of asthma,” the study authors posited. Increased asthma risk also was seen in children of lower socioeconomic status who were exposed to traffic-related pollution or in utero tobacco smoke.

Patients with severe COPD may have lower cognitive performance than patients without COPD, according to a study published in the July 15 American Journal of Respiratory and Critical Care Medicine. “Prior research has suggested an association between COPD and the development of cognitive decline,” the investigators explained. “However, these studies have been cross-sectional or small case series.” The researchers used data from the 1996 to 2002 Health and Retirement Study comprising 4,150 adults (history of COPD, 12%). Compared with participants without COPD, patients with severe and nonsevere COPD had significantly lower mean cognition scores. The association between severe COPD and low cognitive decline remained significant after adjustment for cofactors, but was no longer different for patients with nonsevere COPD.

Patients with sleep-disordered breathing (SDB) may be identified using a simple screening tool in both the clinical and community settings, research findings suggested. “The screening tool consisted of only four variables: sex, blood pressure level, BMI, and self-reported snoring,” the study authors explained in the July Sleep. Of 132 patients visiting one of two hospitals in Japan for a health check and 175 residents of a rural town, the investigators reported an area under the receiver operating characteristic curve of 0.90, a sensitivity of 0.93, and a specificity of 0.66. In addition, they reported an area under the receiver operating characteristic curve of 0.78 for moderate-to-severe SDB and 0.85 for severe SDB. “The diagnostic performance of this tool did not significantly differ from that of previous, more complex tools,” the researchers noted.

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