Eradication of endotracheal tube biofilm by nebulised gentamicin.

Objective: To compare the efficacy of gentamicin, nebulised via the endotracheal tube (ET), with that of parenteral cefotaxime or parenteral cefuroxime in preventing the formation of ET biofilm.

Setting: General intensive care units in two university teaching hospitals.

Design: The microbiology of ET biofilm from 36 ICU patients eligible to receive antibiotic prophylaxis was examined. Peak and trough tracheal concentrations of gentamicin, cefotaxime or cefuroxime were measured in each patient group, on the 2nd day of intubation.

Patients: Twelve patients received gentamicin (80 mg) nebulised in 4 ml normal saline every 8 h, 12 cefotaxime (1 g, 12 hourly) and 12 cefuroxime (750 mg, 8 hourly). Prophylaxis was continued for the duration of intubation.

Measurements and results: Samples of tracheal secretions were taken on the 2nd day of ventilation for determination of antibiotic concentrations. Following extubation, ETs were examined for the presence of biofilm. Pathogens considered to be common aetiological agents for VAP included Staphylococcus aureus, enterococci, Enterobacteriaceae and pseudomonads. While microbial biofilm was found on all ETs from the cephalosporin group, microbial biofilm of these micro-organisms was found on 7 of the 12 ET tubes from patients receiving cefotaxime [S. aureus (4), pseudomonads (1), Enterobacteriaceae (1), enterococcus (1)] and 8 of the 12 ET tubes from patients receiving cefuroxime [Enterobacteriaceae (6), P. aeruginosa (1) and enterococcus (1)]. While microbial biofilm was observed on five ETs from patients receiving nebulised gentamicin, none of these were from pathogens for ventilator-associated pneumonia (VAP). Tracheal concentrations of both cephalosporins were lower than those needed to inhibit the growth of pathogens recovered from ET tube biofilm. The median (and range) concentrations for cefotaxime were 0.90 (<0.23–1.31) mg/l and 0.28 (<0.23–0.58) mg/l for 2 h post-dose and trough samples, respectively. Two hours post-dose concentrations of cefuroxime (median and range) were 0.40 (0.34–0.83) mg/l, with trough concentrations of 0.35 (<0.22–0.47) mg/l. Tracheal concentrations (median and range) of gentamicin measured 1 h post-nebulisation were 790 (352–>1250) mg/l and then, before the next dose, were 436 (250–1000) mg/l.

Conclusion: Nebulised gentamicin attained high concentrations in the ET lumen and was more effective in preventing the formation of biofilm than either parenterally administered cephalosporin and therefore may be effective in preventing this complication of mechanical ventilation.

A randomised, controlled trial of conventional versus automated weaning from mechanical ventilation using SmartcareTM/PS

Objective
Preliminary assessment of an automated weaning system (SmartCare™/PS) compared to usual management of weaning from mechanical ventilation performed in the absence of formal protocols.


Design and setting
A randomised, controlled pilot study in one Australian intensive care unit.


Patients
A total of 102 patients were equally divided between SmartCare/PS and Control.

Interventions
The automated system titrated pressure support, conducted a spontaneous breathing trial and provided notification of success (“separation potential”).

Measurements and results
The median time from the first identified point of suitability for weaning commencement to the state of “separation potential” using SmartCare/PS was 20 h (interquartile range, IQR, 2–40) compared to 8 h (IQR 2–43) with Control (log-rank P = 0.3). The median time to successful extubation was 43 h (IQR 6–169) using SmartCare/PS and 40 (14–87) with Control (log-rank P = 0.6). Unadjusted, the estimated probability of reaching “separation potential” was 21% lower (95% CI, 48% lower to 20% greater) with SmartCare/PS compared to Control. Adjusted for other covariates (age, gender, APACHE II, SOFAmax, neuromuscular blockade, corticosteroids, coma and elevated blood glucose), these estimates were 31% lower (95% CI, 56% lower to 9% greater) with SmartCare/PS. The study groups showed comparable rates of reintubation, non-invasive ventilation post-extubation, tracheostomy, sedation, neuromuscular blockade and use of corticosteroids.

Conclusions
Substantial reductions in weaning duration previously demonstrated were not confirmed when the SmartCare/PS system was compared to weaning managed by experienced critical care specialty nurses, using a 1:1 nurse-to-patient ratio. The effect of SmartCare/PS may be influenced by the local clinical organisational context.

Decisional responsibility for mechanical ventilation and weaning: an international survey

Introduction: Optimal management of mechanical ventilation and weaning requires dynamic and collaborative decision making to minimize complications and avoid delays in the transition to extubation. In the absence of collaboration, ventilation decision making may be fragmented, inconsistent, and delayed. Our objective was to describe the professional group with responsibility for key ventilation and weaning decisions and to examine organizational characteristics associated with nurse involvement.

Methods: A multi-center, cross-sectional, self-administered survey was sent to nurse managers of adult intensive care units (ICUs) in Denmark, Germany, Greece, Italy, Norway, Switzerland, Netherlands and United Kingdom (UK). We summarized data as proportions (95% confidence intervals (CIs)) and calculated odds ratios (OR) to examine ICU organizational variables associated with collaborative decision making.

Results: Response rates ranged from 39% (UK) to 92% (Switzerland), providing surveys from 586 ICUs. Interprofessional collaboration (nurses and physicians) was the most common approach to initial selection of ventilator settings (63% (95% CI 59 to 66)), determination of extubation readiness (71% (67 to 75)), weaning method (73% (69 to 76)), recognition of weaning failure (84% (81 to 87)) and weaning readiness (85% (82 to 87)), and titration of ventilator settings (88% (86 to 91)). A nurse-to-patient ratio other than 1:1 was associated with decreased interprofessional collaboration during titration of ventilator settings (OR 0.2, 95% CI 0.1 to 0.6), weaning method (0.4 (0.2 to 0.9)), determination of extubation readiness (0.5 (0.2 to 0.9)) and weaning failure (0.4 (0.1 to 1.0)). Use of a weaning protocol was associated with increased collaborative decision making for determining weaning (1.8 (1.0 to 3.3)) and extubation readiness (1.9 (1.2 to 3.0)), and weaning method (1.8 (1.1 to 3.0)). Country of ICU location influenced the profile of responsibility for all decisions. Automated weaning modes were used in 55% of ICUs.

Conclusions: Collaborative decision making for ventilation and weaning was employed in most ICUs in all countries although this was influenced by nurse-to-patient ratio, presence of a protocol, and varied across countries. Potential clinical implications of a lack of collaboration include delayed adaptation of ventilation to changing physiological parameters, and delayed recognition of weaning and extubation readiness resulting in unnecessary prolongation of ventilation.

Effect of simvastatin on physiological and biological outcomes in patients undergoing esophagectomy: a randomised placebo controlled trial

OBJECTIVE: To test whether simvastatin improves physiological and biological outcomes in patients undergoing esophagectomy.

BACKGROUND: One-lung ventilation during esophagectomy is associated with inflammation, alveolar epithelial and systemic endothelial injury, and the development of acute lung injury (ALI). Statins that modify many of the underlying processes are a potential therapy to prevent ALI.

METHODS: We conducted a randomized double-blind placebo-controlled trial in patients undergoing esophagectomy. Patients received simvastatin 80 mg or placebo enterally for 4 days preoperatively and 7 days postoperatively. The primary end point was pulmonary dead space (Vd/Vt) at 6 hours after esophagectomy or before extubation. Inflammation was assessed by plasma cytokines and intraoperative exhaled breath condensate pH; alveolar type 1 epithelial injury was assessed by plasma receptor for advanced glycation end products and systemic endothelial injury by the urine albumin-creatinine ratio.

RESULTS: Thirty-nine patients were randomized; 8 patients did not undergo surgery and were excluded. Fifteen patients received simvastatin and 16 received placebo. There was no difference in Vd/Vt or other physiological outcomes. Simvastatin resulted in a significant decrease in plasma MCP-1 on day 3 and reduced exhaled breath condensate acidification. Plasma receptor for advanced glycation end products was significantly lower in the simvastatin-treated group, as was the urine albumin-creatinine ratio on day 7 postsurgery. ALI developed in 4 patients in the placebo group and no patients in the simvastatin group although this difference was not statistically significant (P = 0.1).

CONCLUSIONS: In this proof of concept study, pretreatment with simvastatin in esophagectomy decreased biomarkers of inflammation as well as pulmonary epithelial and systemic endothelial injury.

Automated versus non-automated weaning for reducing the duration of mechanical ventilation for critically ill adults and children: a cochrane systematic review and meta-analysis

IntroductionAutomated weaning systems may improve adaptation of mechanical support for a patient’s ventilatory needs and facilitate systematic and early recognition of their ability to breathe spontaneously and the potential for discontinuation of ventilation. Our objective was to compare mechanical ventilator weaning duration for critically ill adults and children when managed with automated systems versus non-automated strategies. Secondary objectives were to determine differences in duration of ventilation, intensive care unit (ICU) and hospital length of stay (LOS), mortality, and adverse events.MethodsElectronic databases were searched to 30 September 2013 without language restrictions. We also searched conference proceedings; trial registration websites; and article reference lists. Two authors independently extracted data and assessed risk of bias. We combined data using random-effects modelling.ResultsWe identified 21 eligible trials totalling 1,676 participants. Pooled data from 16 trials indicated that automated systems reduced the geometric mean weaning duration by 30% (95% confidence interval (CI) 13% to 45%), with substantial heterogeneity (I2 = 87%, P <0.00001). Reduced weaning duration was found with mixed or medical ICU populations (42%, 95% CI 10% to 63%) and Smartcare/PS™ (28%, 95% CI 7% to 49%) but not with surgical populations or using other systems. Automated systems reduced ventilation duration with no heterogeneity (10%, 95% CI 3% to 16%) and ICU LOS (8%, 95% CI 0% to 15%). There was no strong evidence of effect on mortality, hospital LOS, reintubation, self-extubation and non-invasive ventilation following extubation. Automated systems reduced prolonged mechanical ventilation and tracheostomy. Overall quality of evidence was high.ConclusionsAutomated systems may reduce weaning and ventilation duration and ICU stay. Due to substantial trial heterogeneity an adequately powered, high quality, multi-centre randomized controlled trial is needed.

Automated versus non-automated weaning for reducing the duration of mechanical ventilation in critically ill adults & children (Review)

Background Automated closed loop systems may improve adaptation of mechanical support for a patient's ventilatory needs and facilitate systematic and early recognition of their ability to breathe spontaneously and the potential for discontinuation of ventilation. This review was originally published in 2013 with an update published in 2014. Objectives The primary objective for this review was to compare the total duration of weaning from mechanical ventilation, defined as the time from study randomization to successful extubation (as defined by study authors), for critically ill ventilated patients managed with an automated weaning system versus no automated weaning system (usual care). Secondary objectives for this review were to determine differences in the duration of ventilation, intensive care unit (ICU) and hospital lengths of stay (LOS), mortality, and adverse events related to early or delayed extubation with the use of automated weaning systems compared to weaning in the absence of an automated weaning system. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 8); MEDLINE (OvidSP) (1948 to September 2013); EMBASE (OvidSP) (1980 to September 2013); CINAHL (EBSCOhost) (1982 to September 2013); and the Latin American and Caribbean Health Sciences Literature (LILACS). Relevant published reviews were sought using the Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment Database (HTA Database). We also searched the Web of Science Proceedings; conference proceedings; trial registration websites; and reference lists of relevant articles. The original search was run in August 2011, with database auto-alerts up to August 2012. Selection criteria We included randomized controlled trials comparing automated closed loop ventilator applications to non-automated weaning strategies including non-protocolized usual care and protocolized weaning in patients over four weeks of age receiving invasive mechanical ventilation in an ICU. Data collection and analysis Two authors independently extracted study data and assessed risk of bias. We combined data in forest plots using random-effects modelling. Subgroup and sensitivity analyses were conducted according to a priori criteria. Main results We included 21 trials (19 adult, two paediatric) totaling 1676 participants (1628 adults, 48 children) in this updated review. Pooled data from 16 eligible trials reporting weaning duration indicated that automated closed loop systems reduced the geometric mean duration of weaning by 30% (95% confidence interval (CI) 13% to 45%), however heterogeneity was substantial (I2 = 87%, P < 0.00001). Reduced weaning duration was found with mixed or medical ICU populations (42%, 95% CI 10% to 63%) and Smartcare/PS™ (28%, 95% CI 7% to 49%) but not in surgical populations or using other systems. Automated closed loop systems reduced the duration of ventilation (10%, 95% CI 3% to 16%) and ICU LOS (8%, 95% CI 0% to 15%). There was no strong evidence of an effect on mortality rates, hospital LOS, reintubation rates, self-extubation and use of non-invasive ventilation following extubation. Prolonged mechanical ventilation > 21 days and tracheostomy were reduced in favour of automated systems (relative risk (RR) 0.51, 95% CI 0.27 to 0.95 and RR 0.67, 95% CI 0.50 to 0.90 respectively). Overall the quality of the evidence was high with the majority of trials rated as low risk. Authors' conclusions Automated closed loop systems may result in reduced duration of weaning, ventilation and ICU stay. Reductions are more likely to occur in mixed or medical ICU populations. Due to the lack of, or limited, evidence on automated systems other than Smartcare/PS™ and Adaptive Support Ventilation no conclusions can be drawn regarding their influence on these outcomes. Due to substantial heterogeneity in trials there is a need for an adequately powered, high quality, multi-centre randomized controlled trial in adults that excludes 'simple to wean' patients. There is a pressing need for further technological development and research in the paediatric population.

Total colonic dye-spray increases the detection of diminutive adenomas during routine colonoscopy:a randomized controlled trial

Background: Small adenomas may be missed during colonoscopy, but chromoscopy has been reported to enhance detection. The aim of this randomized-controlled trial was to determine the effect of total colonic dye spray on adenoma detection during routine colonoscopy.

Methods: Consecutive outpatients undergoing routine colonoscopy were randomized to a dye-spray group (0.1% indigo carmine used to coat the entire colon during withdrawal from the cecum) or control group (no dye).

Results: Two hundred fifty-nine patients were randomized, 124 to the dye-spray and 135 to the control group; demographics, indication for colonoscopy, and quality of the preparation were similar between the groups. Extubation from the cecum took a median of 9:05 minutes (range: 2:4824:44 min) in the dye-spray group versus 4:52 minutes (range: 1:42-15:21 min] in the control group (p <0.0001). The proportion of patients with at least 1 adenoma and the total number of adenomas were not different between groups. However, in the dye-spray group significantly more diminutive adenomas (

Conclusions: Dye-spray increases the detection of small adenomas in the proximal colon and patients with multiple adenomas, but long-term outcomes should be studied to determine the clinical value of these findings.

Alpha-2 agonists for sedation of mechanically ventilated adults in intensive care units: a systematic review

BACKGROUND: Care of critically ill patients in intensive care units (ICUs) often requires potentially invasive or uncomfortable procedures, such as mechanical ventilation (MV). Sedation can alleviate pain and discomfort, provide protection from stressful or harmful events, prevent anxiety and promote sleep. Various sedative agents are available for use in ICUs. In the UK, the most commonly used sedatives are propofol (Diprivan(®), AstraZeneca), benzodiazepines [e.g. midazolam (Hypnovel(®), Roche) and lorazepam (Ativan(®), Pfizer)] and alpha-2 adrenergic receptor agonists [e.g. dexmedetomidine (Dexdor(®), Orion Corporation) and clonidine (Catapres(®), Boehringer Ingelheim)]. Sedative agents vary in onset/duration of effects and in their side effects. The pattern of sedation of alpha-2 agonists is quite different from that of other sedatives in that patients can be aroused readily and their cognitive performance on psychometric tests is usually preserved. Moreover, respiratory depression is less frequent after alpha-2 agonists than after other sedative agents.

OBJECTIVES: To conduct a systematic review to evaluate the comparative effects of alpha-2 agonists (dexmedetomidine and clonidine) and propofol or benzodiazepines (midazolam and lorazepam) in mechanically ventilated adults admitted to ICUs.

DATA SOURCES: We searched major electronic databases (e.g. MEDLINE without revisions, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE and Cochrane Central Register of Controlled Trials) from 1999 to 2014.

METHODS: Evidence was considered from randomised controlled trials (RCTs) comparing dexmedetomidine with clonidine or dexmedetomidine or clonidine with propofol or benzodiazepines such as midazolam, lorazepam and diazepam (Diazemuls(®), Actavis UK Limited). Primary outcomes included mortality, duration of MV, length of ICU stay and adverse events. One reviewer extracted data and assessed the risk of bias of included trials. A second reviewer cross-checked all the data extracted. Random-effects meta-analyses were used for data synthesis.

RESULTS: Eighteen RCTs (2489 adult patients) were included. One trial at unclear risk of bias compared dexmedetomidine with clonidine and found that target sedation was achieved in a higher number of patients treated with dexmedetomidine with lesser need for additional sedation. The remaining 17 trials compared dexmedetomidine with propofol or benzodiazepines (midazolam or lorazepam). Trials varied considerably with regard to clinical population, type of comparators, dose of sedative agents, outcome measures and length of follow-up. Overall, risk of bias was generally high or unclear. In particular, few trials blinded outcome assessors. Compared with propofol or benzodiazepines (midazolam or lorazepam), dexmedetomidine had no significant effects on mortality [risk ratio (RR) 1.03, 95% confidence interval (CI) 0.85 to 1.24, I (2) = 0%; p = 0.78]. Length of ICU stay (mean difference -1.26 days, 95% CI -1.96 to -0.55 days, I (2) = 31%; p = 0.0004) and time to extubation (mean difference -1.85 days, 95% CI -2.61 to -1.09 days, I (2) = 0%; p < 0.00001) were significantly shorter among patients who received dexmedetomidine. No difference in time to target sedation range was observed between sedative interventions (I (2) = 0%; p = 0.14). Dexmedetomidine was associated with a higher risk of bradycardia (RR 1.88, 95% CI 1.28 to 2.77, I (2) = 46%; p = 0.001).

LIMITATIONS: Trials varied considerably with regard to participants, type of comparators, dose of sedative agents, outcome measures and length of follow-up. Overall, risk of bias was generally high or unclear. In particular, few trials blinded assessors.

CONCLUSIONS: Evidence on the use of clonidine in ICUs is very limited. Dexmedetomidine may be effective in reducing ICU length of stay and time to extubation in critically ill ICU patients. Risk of bradycardia but not of overall mortality is higher among patients treated with dexmedetomidine. Well-designed RCTs are needed to assess the use of clonidine in ICUs and identify subgroups of patients that are more likely to benefit from the use of dexmedetomidine.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42014014101.

FUNDING: The National Institute for Health Research Health Technology Assessment programme. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates.

Weaning from ventilation

Aims/purpose: Getting off the ventilator is an important patient-centred outcome for patients with acute respiratory failure. It signifies an improvement in patient condition, enables easier communication, reduces fear and anxiety and consequently a reduced requirement for sedatives. Weaning from ventilation therefore is a core ICU nursing task that is addressed in this presentation.
Presentation description: There are different schools of thought on when ventilator weaning begins including: (a) from intubation with titration of support; and (b) only when the patient’s condition improves. There are also different schools of thought on how to wean including gradual reductions in ventilator support to: (a) a low level consistent with extubation; or (b) to a level to attempt a spontaneous breathing trial followed by extubation if successful. Regardless of the approach, what is patient-relevant is the need to determine early when the patient may be ‘ready’ to discontinue ventilation. This time point can be assessed using simple criteria and should involve all ICU staff to the level of their experience. This presentation challenges the notion that only senior nurses or nurses with a ‘weaning course’ should be involved in the weaning process and proposes opportunities for engaging nurses with all levels of experience.
Conclusion: An ICU nursing taskforce that is focused and engaged in determining patient readiness for weaning can make a strong contribution to patient-relevant outcomes.