Evaluation of interleukin-6 and its soluble receptor components sIL-6R and sgp130 as markers of inflammation in inflammatory bowel diseases

Purpose

Interleukin-6 (IL-6) production and signalling are increased in the inflamed mucosa in inflammatory bowel diseases (IBD). As published serum levels of IL-6 and its soluble receptors sIL-6R and sgp130 in IBD are from small cohorts and partly contradictory, we systematically evaluated IL-6, sIL-6R and sgp130 levels as markers of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC).

Methods

Consecutive adult outpatients with confirmed CD or UC were included, and their disease activity and medication were monitored. Serum from 212 CD patients (815 measurements) and 166 UC patients (514 measurements) was analysed, and 100 age-matched healthy blood donors were used as controls.

Results

IL-6 serum levels were significantly elevated in active versus inactive CD and UC, also compared with healthy controls. However, only a fraction of IBD patients showed increased serum IL-6. IL-6 levels ranged up to 32.7 ng/mL in active CD (>?5000-fold higher than in controls), but also up to 6.9 ng/mL in inactive CD. Increases in active UC (up to 195 pg/mL) and inactive UC (up to 27 pg/mL) were less pronounced. Associations between IL-6 serum levels and C-reactive protein concentrations as well as leukocyte and thrombocyte counts were observed. Median sIL-6R and sgp130 levels were only increased by up to 15%, which was considered of no diagnostic significance.

Conclusions

Only a minority of IBD patients shows elevated IL-6 serum levels. However, in these patients, IL-6 is strongly associated with disease activity. Its soluble receptors sIL-6R and sgp130 do not appear useful as biomarkers in IBD.

     

Developing research priorities for nurses working in the gynaecology setting in Western Australia

Background

Nurses working in clinical settings are instrumental to translating research into practice. The Delphi approach has been used by clinicians worldwide to set research agendas relevant to their clinical work.

A work-life perspective on sleep and fatigue—looking beyond shift workers

This study examines sleep and fatigue through a work-life lens. Whilst most often thought of as an issue for shift workers, this study observed that self-reported insufficient sleep and fatigue were prevalent for workers on standard daytime schedules. Using a representative sample of 573 daytime workers (51.3% men; 70.7% aged 25−54 yr) from one Australian state, it was observed that 26.4% of daytime workers never or rarely get the seven hours of sleep a night that is recommended for good health. Those with parenting responsibilites (29.4%) or working long (45+) hours (37.4%) were most likely to report insufficient sleep. Whereas mothers in full-time work were most likely to report frequent fatigue (42.5%). This study highlights the common experience of insufficient sleep and fatigue in a daytime workforce, with significant implications for health and safety at work and outside of work. Stronger and more effective legislation addressing safe and ‘decent’ working time is clearly needed, along with greater awareness and acceptance within workplace cultures of the need to support reasonable workloads and working hours.     

Retrospective Review of Critically Ill Patients Experiencing Alcohol Withdrawal: Dexmedetomidine Versus Propofol and/or Lorazepam Continuous Infusions

Background:

Alcohol withdrawal symptoms can be difficult to manage and may lead to an intensive care unit (ICU) admission. Patients experiencing severe alcohol withdrawal often require high doses of sedatives, which can lead to respiratory depression and the need for endotracheal intubation. Dexmedetomidine, an alpha-2 adrenoreceptor agonist, provides adequate sedation with little effect on respiratory function when compared to other sedatives.

Objective:

To evaluate sedation with a continuous infusion of dexmedetomidine versus propofol and/or lorazepam in critically ill patients experiencing alcohol withdrawal.

Methods:

A retrospective chart review was conducted on ICU admissions between March 2002 and April 2009 for alcohol withdrawal patients who necessitated treatment with a continuous infusion of dexmedetomidine, propofol, and/or lorazepam. Primary outcomes included the incidence of mechanical ventilation, length of mechanical ventilation (if applicable), and ICU and hospital length of stay.

Results:

Fifteen patients were treated with a continuous infusion of dexmedetomidine, and 17 were treated with an infusion of propofol and/or lorazepam. Two patients (13.3%) required intubation and mechanical ventilation in the dexmedetomidine group versus 10 (58.8%) in the propofol and/or lorazepam group (P = .006). Length of stay in the ICU was 53 hours for patients treated with dexmedetomidine versus 114.9 hours in the propofol and/or lorazepam group (P = .016). Hospital length of stay was less for the dexmedetomidine group, 135.8 hours versus 241.1 hours in the propofol and/or lorazepam group (P = .008).

Conclusions:

Dexmedetomidine use was associated with a decrease in the incidence of endotracheal intubation when used to sedate patients experiencing alcohol withdrawal. Patients transferred to a lower level of care faster and were discharged from the hospital sooner when treated with dexmedetomidine.Key Words: alcohol, dexmedetomidine, lorazepam, propofol, withdrawalThere are approximately 18.3 million people in the United States dependent on or abusing alcohol and 2.9 million people requiring treatment for problems related to alcohol use.¹ The impact of alcohol withdrawal syndrome can be devastating, both physically and neurologically. The syndrome can include headache, anxiety, hallucinations, nausea and vomiting, sweating, seizures, irritability, and the most severe form of alcohol withdrawal, delirium tremens. Patients experiencing delirium tremens have a mortality rate of up to 5%.² The American Society of Addiction Medicine guidelines for the management of alcohol withdrawal delirium recommend sedative-hypnotic drugs, such as benzodiazepines, as the primary agents for managing alcohol withdrawal syndrome.³The goal of alcohol withdrawal treatment is to relieve the patients’ agitation and prevent the further development of more severe symptoms. Some patients may experience symptoms such as increased levels of anxiety, hallucinations, and delirium tremens. In these severe cases, escalating benzodiazepine doses (to include initiation of a continuous infusion) or initiation of another sedative, such as propofol or phenobarbital, becomes necessary to control agitation. The use of sedatives can cause a decrease in respiratory drive, which can lead to patients requiring transfer to a higher level of care with the potential for intubation and mechanical ventilator support.At North Colorado Medical Center (NCMC), patients undergoing alcohol withdrawal are initially treated with benzodiazepines. If escalating doses of benzodiazepines are unable to control agitation and other alcohol withdrawal symptoms, patients are evaluated by the physician for transfer to the intensive care unit (ICU). In the past, the standard of care in the NCMC ICU for patients experiencing severe alcohol withdrawal not controlled by intermittent benzodiazepines was the initiation of a benzodiazepine and/or propofol infusion based on the physician’s assessment and preference. Often these patients required intubation and mechanical ventilation. Recently, however, the sedation of patients experiencing severe alcohol withdrawal is increasingly being managed with dexmedetomidine in the ICU at NCMC.Clonidine has historically been used for treatment and prophylaxis of the symptoms of alcohol withdrawal.^3–9 Dexmedetomidine is a centrally acting, relatively selective, alpha2-adrenergic agonist similar to clonidine with sedative and analgesic properties. Dexmedetomidine reduces the stress response, decreases norepinephrine and epinephrine levels, and attenuates increases in heart rate and blood pressure without depressing the respiratory drive.^10,11The use of dexmedetomidine has been noted in multiple case reports, case series, and one small randomized controlled trial as a possibly effective agent for the management of alcohol withdrawal.^12–19 The case reports and case series primarily reported on safety, reduced benzodiazepine doses, and reduced delirium scores in the use of dexmedetomidine in alcohol withdrawal patients. The one randomized, blinded, placebo-controlled trial published to date by Mueller et al compared dexmedetomidine to placebo in patients with severe alcohol withdrawal. The primary endpoint was benzodiazepine requirements in the first 24 hours and cumulative dose over the first 7 days of hospitalization. They reported a reduced 24-hour benzodiazepine dose in the dexmedetomidine group and no difference in the 7-day cumulative dose between groups.¹²One of the main advantages of dexmedetomidine is that it does not cause respiratory depression.¹¹ This is especially important in patients admitted to the ICU for severe alcohol withdrawal. Studies have demonstrated that patients admitted to the ICU with severe alcohol withdrawal have a high rate of intubation, reportedly 22% to 65%.²⁰ Ventilator-associated pneumonia (VAP) can occur in 10% to 20% of patients receiving greater than 48 hours of mechanical ventilation. Patients who contract VAP have increased hospital costs of more than $10,000 per day, increased ICU length of stay by 5 to 7 days, and, in some reports, increased mortality.²¹ Furthermore, intubation and mechanical ventilation on ICU day 1 has been recognized as a predictor of a longer length of hospital stay.²²Assessment and documentation of the effectiveness of dexmedetomidine for treatment of alcohol withdrawal, while growing rapidly, is still lacking in the medical literature. The purpose of this retrospective observational study was to evaluate the incidence and duration of mechanical ventilation and the length of ICU and hospital stay in alcohol withdrawal patients treated with dexmedetomidine, propofol, and/or lorazepam continuous infusions.