Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials

Long-term sedation with midazolam or propofol in intensive care units (ICUs) has serious adverse effects. Dexmedetomidine, an α(2)-agonist available for ICU sedation, may reduce the duration of mechanical ventilation and enhance patient comfort.

Intensive care sedation: the past, present and the future

Despite the universal prescription of sedative drugs in the intensive care unit (ICU), current practice is not guided by high-level evidence. Landmark sedation trials have made significant contributions to our understanding of the problems associated with ICU sedation and have promoted changes to current practice. We identified challenges and limitations of clinical trials which reduced the generalizability and the universal adoption of key interventions. We present an international perspective regarding current sedation practice and a blueprint for future research, which seeks to avoid known limitations and generate much-needed high-level evidence to better guide clinicians' management and therapeutic choices of sedative agents.

Dexmedetomidine versus standard care sedation with propofol or midazolam in intensive care: an economic evaluation.

INTRODUCTION Dexmedetomidine was shown in two European randomized double-blind double-dummy trials (PRODEX and MIDEX) to be non-inferior to propofol and midazolam in maintaining target sedation levels in mechanically ventilated intensive care unit (ICU) patients. Additionally, dexmedetomidine shortened the time to extubation versus both standard sedatives, suggesting that it may reduce ICU resource needs and thus lower ICU costs. Considering resource utilization data from these two trials, we performed a secondary, cost-minimization analysis assessing the economics of dexmedetomidine versus standard care sedation. METHODS The total ICU costs associated with each study sedative were calculated on the basis of total study sedative consumption and the number of days patients remained intubated, required non-invasive ventilation, or required ICU care without mechanical ventilation. The daily unit costs for these three consecutive ICU periods were set to decline toward discharge, reflecting the observed reduction in mean daily Therapeutic Intervention Scoring System (TISS) points between the periods. A number of additional sensitivity analyses were performed, including one in which the total ICU costs were based on the cumulative sum of daily TISS points over the ICU period, and two further scenarios, with declining direct variable daily costs only. RESULTS Based on pooled data from both trials, sedation with dexmedetomidine resulted in lower total ICU costs than using the standard sedatives, with a difference of €2,656 in the median (interquartile range) total ICU costs-€11,864 (€7,070 to €23,457) versus €14,520 (€7,871 to €26,254)-and €1,649 in the mean total ICU costs. The median (mean) total ICU costs with dexmedetomidine compared with those of propofol or midazolam were €1,292 (€747) and €3,573 (€2,536) lower, respectively. The result was robust, indicating lower costs with dexmedetomidine in all sensitivity analyses, including those in which only direct variable ICU costs were considered. The likelihood of dexmedetomidine resulting in lower total ICU costs compared with pooled standard care was 91.0% (72.4% versus propofol and 98.0% versus midazolam). CONCLUSIONS From an economic point of view, dexmedetomidine appears to be a preferable option compared with standard sedatives for providing light to moderate ICU sedation exceeding 24 hours. The savings potential results primarily from shorter time to extubation. TRIAL REGISTRATION ClinicalTrials.gov NCT00479661 (PRODEX), NCT00481312 (MIDEX).

Adoption of a sedation scoring system and sedation guideline in an intensive care unit

Aim. The paper presents a study assessing the rate of adoption of a sedation scoring system and sedation guideline. Background. Clinical practice guidelines including sedation guidelines have been shown to improve patient outcomes by standardizing care. In particular sedation guidelines have been shown to be beneficial for intensive care patients by reducing the duration of ventilation. Despite the acceptance that clinical practice guidelines are beneficial, adoption rates are rarely measured. Adoption data may reveal other factors which contribute to improved outcomes. Therefore, the usefulness of the guideline may be more appropriately assessed by collecting adoption data. Method. A quasi-experimental pre-intervention and postintervention quality improvement design was used. Adoption was operationalized as documentation of sedation score every 4 hours and use of the sedation and analgesic medications suggested in the guideline. Adoption data were collected from patients' charts on a random day of the month; all patients in the intensive care unit on that day were assigned an adoption category. Sedation scoring system adoption data were collected before implementation of a sedation guideline, which was implemented using an intensive information-giving strategy, and guideline adoption data were fed back to bedside nurses. After implementation of the guideline, adoption data were collected for both the sedation scoring system and the guideline. The data were collected in the years 2002-2004. Findings. The sedation scoring system was not used extensively in the pre-intervention phase of the study; however, this improved in the postintervention phase. The findings suggest that the sedation guideline was gradually adopted following implementation in the postintervention phase of the study. Field notes taken during the implementation of the sedation scoring system and the guideline reveal widespread acceptance of both. Conclusion. Measurement of adoption is a complex process. Appropriate operationalization contributes to greater accuracy. Further investigation is warranted to establish the intensity and extent of implementation required to positively affect patient outcomes.

Effect of sedation level on the prevalence of delirium when assessed with CAM-ICU and ICDSC

Purpose We hypothesized that reduced arousability (Richmond Agitation Sedation Scale, RASS, scores −2 to −3) for any reason during delirium assessment increases the apparent prevalence of delirium in intensive care patients. To test this hypothesis, we assessed delirium using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and Intensive Care Delirium Screening Checklist (ICDSC) in intensive care patients during sedation stops, and related the findings to the level of sedation, as assessed with RASS score. Methods We assessed delirium in 80 patients with ICU stay longer than 48 h using CAM-ICU and ICDSC during daily sedation stops. Sedation was assessed using RASS. The effect of including patients with a RASS of −2 and −3 during sedation stop (“light to moderate sedation”, eye contact less than 10 s or not at all, respectively) on prevalence of delirium was analyzed. Results A total of 467 patient days were assessed. The proportion of CAM-ICU-positive evaluations decreased from 53 to 31 % (p < 0.001) if assessments from patients at RASS −2/−3 (22 % of all assessments) were excluded. Similarly, the number of positive ICDSC results decreased from 51 to 29 % (p < 0.001). Conclusions Sedation per se can result in positive items of both CAM-ICU and ICDSC, and therefore in a diagnosis of delirium. Consequently, apparent prevalence of delirium is dependent on how a depressed level of consciousness after sedation stop is interpreted (delirium vs persisting sedation). We suggest that any reports on delirium using these assessment tools should be stratified for a sedation score during the assessment.

DESCRIBING SLEEP AND SEDATION PRACTICES IN THE ICU: A MULTINATIONAL SURVEY

Introduction Sleep disturbances are common in critically ill patients treated in the intensive care unit (ICU) with the potential for serious consequences and long-term effects on health outcomes and patient morbidity.
Objectives Our aim was to describe sleep management and sedation practices of adult ICUs in ten countries and to evaluate roles and responsibilities of the ICU staff in relation to key sleep and sedation decisions.
Methods A multicenter, self-administered survey sent to nurse managers of adult ICUs across 10 countries. The questionnaire comprised four domains: sleep characteristics of the critically ill; sleep and sedation practices; non-pharmacological and pharmacological interventions used to improve sleep; and the autonomy and influence of nurses on sleeping practices in the ICU.
Results Overall response rate was 66% (range 32% UK to 100% Cyprus), providing data from 522 ICUs. In all countries, the most frequent patient characteristic perceived to identify sleep was lying quietly with closed eyes (N=409, 78%) (range 92% Denmark to 36% Italy). The most commonly used sedation scale was the Richmond Agitation-Sedation Score (RASS) (N=220, 42%) (range 81% UK to 0% Denmark, Cyprus where most ICUs used the Ramsay score). In most ICUs, selection of sleep medication (N=265, 51%) and assessment of effect (N=309, 59%) was performed by physicians and nurses based on collaborative discussion. In a minority of ICUs (N=161, 31%), decisions and assessments were made by physicians alone. The most commonly used (in all countries) non-pharmacological intervention to promote sleep was reducing ICU staff noise (N=473, 91%) (range 100% Denmark, Norway to 78% Canada). Only 95 ICUs (18%) used earplugs on a frequent basis (range 0% Greece, Cyprus, Denmark to 57% Sweden). Propofol was the drug used most commonly for sedation (N=359, 69%) (range 96% Sweden to 29% Canada). Chloral hydrate was used by only 63 (12%) ICUs (range 0% Greece, Cyprus, Denmark, Italy to 56% Germany). Sedation scales were used on a routine basis by 77% of the 522 ICUs. Participants scored nursing autonomy for sleep and sedation management as moderate; median score of 5 (scale of 0 to 10), range 7 (Canada, Greece, Sweden) to 4 (Norway, Poland). Nursing influence on sleep and sedation decisions was perceived considerable; median score 8, range 9 (Denmark) to 5 (Poland).
Conclusions We found considerable across country variation in sleep promotion and sedation management practices though most have adopted a sedation scale as recommended in professional society guidelines. Most ICUs in all countries used a range of pharmacological and non-pharmacological interventions to promote sleep. Most units reported inter-professional decision-making with nurses perceived to have substantial influence on sleep/sedation decisions.

Part 1. Chemical and Physical Restraints in the Management of Mechanically Ventilated Patients in the ICU: Contributing Factors

Chemical and physical restraints are frequently used in the intensive care unit (ICU) to control agitated patients and to prevent self-harm and unplanned extubations. Published work relating to the numerous issues of the care and treatment strategies for these patients remains conflicting and unclear. Literature regarding sedation and chemical restraint reveals a trend towards management with lighter sedation, use of sedation assessment tools and sedation protocols. It remains unclear which treatment is best for agitated and delirious patients, and the evidence on the effect of sedation is conflicting. A large portion of the literature on the use of physical restraint is from general hospital wards and residential homes, and not from the ICU environment. The purpose of this paper is to provide a summary of the existing literature on the use of physical and chemical restraints in the ICU setting. In Part 1 of this two-part paper, the evidence on chemical and physical restraints is explored with specific focus on definition of terms, unplanned

Part 2. Chemical and physical restraints in the management of mechanically ventilated patients in the ICU: A patient perspective

An important goal of the care for the mechanically ventilated patient is to minimize patient discomfort and anxiety. This is partly achieved by frequent use of chemical and physical restraints. The majority of patients in intensive care will receive some form of sedation. The goal and use of sedation has changed considerably over the past few decades with literature evidencing trends toward overall lighter sedation levels and daily interruption of sedation. Conversely, the use of physical restraint for the ventilated patient in ICU differs considerably between nations and continents. A large portion of the literature on the use of physical restraint is from general hospital wards and residential homes, and not from the ICU environment. Recent literature suggests minimal use of physical restraint in the ICU, and that reduction programmes have been initiated. However, very few papers illuminate the patient's experience of physical and chemical restraints as a treatment strategy. In Part 1 of this two-part review, the evidence on chemical and physical restraints was explored with specific focus on definitions of terms, unplanned extubation, agitation, delirium as well as the impact of nurse–patient ratios in the ICU on these issues. This paper, Part 2, examines the evidence related to chemical and physical restraints from the mechanically ventilated patient's perspective.

Nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory : a mixed methods study

The cardiac catheterisation laboratory (CCL) is a specialised medical radiology facility where both chronic-stable and life-threatening cardiovascular illness is evaluated and treated. Although there are many potential sources of discomfort and distress associated with procedures performed in the CCL, a general anaesthetic is not usually required. For this reason, an anaesthetist is not routinely assigned to the CCL. Instead, to manage pain, discomfort and anxiety during the procedure, nurses administer a combination of sedative and analgesic medications according to direction from the cardiologist performing the procedure. This practice is referred to as nurse-administered procedural sedation and analgesia (PSA). While anecdotal evidence suggested that nurse-administered PSA was commonly used in the CCL, it was clear from the limited information available that current nurse-led PSA administration and monitoring practices varied and that there was contention around some aspects of practice including the type of medications that were suitable to be used and the depth of sedation that could be safely induced without an anaesthetist present. The overall aim of the program of research presented in this thesis was to establish an evidence base for nurse-led sedation practices in the CCL context. A sequential mixed methods design was used over three phases. The objective of the first phase was to appraise the existing evidence for nurse-administered PSA in the CCL. Two studies were conducted. The first study was an integrative review of empirical research studies and clinical practice guidelines focused on nurse-administered PSA in the CCL as well as in other similar procedural settings. This was the first review to systematically appraise the available evidence supporting the use of nurse-administered PSA in the CCL. A major finding was that, overall, nurse-administered PSA in the CCL was generally deemed to be safe. However, it was concluded from the analysis of the studies and the guidelines that were included in the review, that the management of sedation in the CCL was impacted by a variety of contextual factors including local hospital policy, workforce constraints and cardiologists’ preferences for the type of sedation used. The second study in the first phase was conducted to identify a sedation scale that could be used to monitor level of sedation during nurse-administered PSA in the CCL. It involved a structured literature review and psychometric analysis of scale properties. However, only one scale was found that was developed specifically for the CCL, which had not undergone psychometric testing. Several weaknesses were identified in its item structure. Other sedation scales that were identified were developed for the ICU. Although these scales have demonstrated validity and reliability in the ICU, weaknesses in their item structure precluded their use in the CCL. As findings indicated that no existing sedation scale should be applied to practice in the CCL, recommendations for the development and psychometric testing of a new sedation scale were developed. The objective of the second phase of the program of research was to explore current practice. Three studies were conducted in this phase using both quantitative and qualitative research methods. The first was a qualitative explorative study of nurses’ perceptions of the issues and challenges associated with nurse-administered PSA in the CCL. Major themes emerged from analysis of the qualitative data regarding the lack of access to anaesthetists, the limitations of sedative medications, the barriers to effective patient monitoring and the impact that the increasing complexity of procedures has on patients' sedation requirements. The second study in Phase Two was a cross-sectional survey of nurse-administered PSA practice in Australian and New Zealand CCLs. This was the first study to quantify the frequency that nurse-administered PSA was used in the CCL setting and to characterise associated nursing practices. It was found that nearly all CCLs utilise nurse-administered PSA (94%). Of note, by characterising nurse-administered PSA in Australian and New Zealand CCLs, several strategies to improve practice, such as setting up protocols for patient monitoring and establishing comprehensive PSA education for CCL nurses, were identified. The third study in Phase Two was a matched case-control study of risk factors for impaired respiratory function during nurse-administered PSA in the CCL setting. Patients with acute illness were found to be nearly twice as likely to experience impaired respiratory function during nurse-administered PSA (OR=1.78; 95%CI=1.19-2.67; p=0.005). These significant findings can now be used to inform prospective studies investigating the effectiveness of interventions for impaired respiratory function during nurse-administered PSA in the CCL. The objective of the third and final phase of the program of research was to develop recommendations for practice. To achieve this objective, a synthesis of findings from the previous phases of the program of research informed a modified Delphi study, which was conducted to develop a set of clinical practice guidelines for nurse-administered PSA in the CCL. The clinical practice guidelines that were developed set current best practice standards for pre-procedural patient assessment and risk screening practices as well as the intra and post-procedural patient monitoring practices that nurses who administer PSA in the CCL should undertake in order to deliver safe, evidence-based and consistent care to the many patients who undergo procedures in this setting. In summary, the mixed methods approach that was used clearly enabled the research objectives to be comprehensively addressed in an informed sequential manner, and, as a consequence, this thesis has generated a substantial amount of new knowledge to inform and support nurse-led sedation practice in the CCL context. However, a limitation of the research to note is that the comprehensive appraisal of the evidence conducted, combined with the guideline development process, highlighted that there were numerous deficiencies in the evidence base. As such, rather than being based on high-level evidence, many of the recommendations for practice were produced by consensus. For this reason, further research is required in order to ascertain which specific practices result in the most optimal patient and health service outcomes. Therefore, along with necessary guideline implementation and evaluation projects, post-doctoral research is planned to follow up on the research gaps identified, which are planned to form part of a continuing program of research in this field.

A review of sedation scales for the cardiac catheterization laboratory

Sedation scales have the potential to facilitate effective procedural sedation and analgesia in the cardiac catheterization laboratory (CCL). For this potential to become realised, a scale that is suitable for use in the CCL either needs to be identified or developed. To identify sedation scales, a review of Medline and CINHAL was conducted. One sedation scale for the CCL, the NASPE SED, and 15 Intensive Care Unit (ICU) scales met the inclusion and exclusion criteria. Analysis of the scale’s item structures and psychometric properties was then performed. None of these scales were deemed suitable for use in the CCL. As such, further research is required to develop a new scale. The new scale should consist of more than one item because it will be the most effective for tracking the patient’s response to medications. Specific tests required to conduct a rigorous evaluation of the new scale’s psychometric properties are outlined in this paper.

Development of process control methodology for tracking the quality and safety of pain, agitation and sedation management in critical care units

Objective: To develop sedation, pain, and agitation quality measures using process control methodology and evaluate their properties in clinical practice. Design: A Sedation Quality Assessment Tool was developed and validated to capture data for 12-hour periods of nursing care. Domains included pain/discomfort and sedation-agitation behaviors; sedative, analgesic, and neuromuscular blocking drug administration; ventilation status; and conditions potentially justifying deep sedation. Predefined sedation-related adverse events were recorded daily. Using an iterative process, algorithms were developed to describe the proportion of care periods with poor limb relaxation, poor ventilator synchronization, unnecessary deep sedation, agitation, and an overall optimum sedation metric. Proportion charts described processes over time (2 monthly intervals) for each ICU. The numbers of patients treated between sedation-related adverse events were described with G charts. Automated algorithms generated charts for 12 months of sequential data. Mean values for each process were calculated, and variation within and between ICUs explored qualitatively. Setting: Eight Scottish ICUs over a 12-month period. Patients: Mechanically ventilated patients. Interventions: None. Measurements and Main Results: The Sedation Quality Assessment Tool agitation-sedation domains correlated with the Richmond Sedation Agitation Scale score (Spearman [rho] = 0.75) and were reliable in clinician-clinician (weighted kappa; [kappa] = 0.66) and clinician-researcher ([kappa] = 0.82) comparisons. The limb movement domain had fair correlation with Behavioral Pain Scale ([rho] = 0.24) and was reliable in clinician-clinician ([kappa] = 0.58) and clinician-researcher ([kappa] = 0.45) comparisons. Ventilator synchronization correlated with Behavioral Pain Scale ([rho] = 0.54), and reliability in clinician-clinician ([kappa] = 0.29) and clinician-researcher ([kappa] = 0.42) comparisons was fair-moderate. Eight hundred twenty-five patients were enrolled (range, 59-235 across ICUs), providing 12,385 care periods for evaluation (range 655-3,481 across ICUs). The mean proportion of care periods with each quality metric varied between ICUs: excessive sedation 12-38%; agitation 4-17%; poor relaxation 13-21%; poor ventilator synchronization 8-17%; and overall optimum sedation 45-70%. Mean adverse event intervals ranged from 1.5 to 10.3 patients treated. The quality measures appeared relatively stable during the observation period. Conclusions: Process control methodology can be used to simultaneously monitor multiple aspects of pain-sedation-agitation management within ICUs. Variation within and between ICUs could be used as triggers to explore practice variation, improve quality, and monitor this over time

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.

Hypertriglyceridemia: a potential side effect of propofol sedation in critical illness

Hypertriglyceridemia (hyperTG) is common among intensive care unit (ICU) patients, but knowledge about hyperTG risk factors is scarce. The present study aims to identify risk factors favoring its development in patients requiring prolonged ICU treatment.

Sedation and weaning from mechanical ventilation: effects of process optimization outside a clinical trial

PURPOSE: We studied the effects of reorganization and changes in the care process, including use of protocols for sedation and weaning from mechanical ventilation, on the use of sedative and analgesic drugs and on length of respiratory support and stay in the intensive care unit (ICU). MATERIALS AND METHODS: Three cohorts of 100 mechanically ventilated ICU patients, admitted in 1999 (baseline), 2000 (implementation I, after a change in ICU organization and in diagnostic and therapeutic approaches), and 2001 (implementation II, after introduction of protocols for weaning from mechanical ventilation and sedation), were studied retrospectively. RESULTS: Simplified Acute Physiology Score II (SAPS II), diagnostic groups, and number of organ failures were similar in all groups. Data are reported as median (interquartile range).Time on mechanical ventilation decreased from 18 (7-41) (baseline) to 12 (7-27) hours (implementation II) (P = .046), an effect which was entirely attributable to noninvasive ventilation, and length of ICU stay decreased in survivors from 37 (21-71) to 25 (19-63) hours (P = .049). The amount of morphine (P = .001) and midazolam (P = .050) decreased, whereas the amount of propofol (P = .052) and fentanyl increased (P = .001). Total Therapeutic Intervention Scoring System-28 (TISS-28) per patient decreased from 137 (99-272) to 113 (87-256) points (P = .009). Intensive care unit mortality was 19% (baseline), 8% (implementation I), and 7% (implementation II) (P = .020). CONCLUSIONS: Changes in organizational and care processes were associated with an altered pattern of sedative and analgesic drug prescription, a decrease in length of (noninvasive) respiratory support and length of stay in survivors, and decreases in resource use as measured by TISS-28 and mortality.