M.H.W.A. van den Boogaard

Development and validation of PRE-DELIRIC (PREdiction of DELIRium in ICu patients) delirium prediction model for intensive care patients: observational multicentre study

Objectives To develop and validate a delirium prediction model for adult intensive care patients and determine its additional value compared with prediction by caregivers. Design Observational multicentre study. Setting Five intensive care units in the Netherlands (two university hospitals and three university affiliated teaching hospitals). Participants 3056 intensive care patients aged 18 years or over. Main outcome measure Development of delirium (defined as at least one positive delirium screening) during patients’ stay in intensive care. Results The model was developed using 1613 consecutive intensive care patients in one hospital and temporally validated using 549 patients from the same hospital. For external validation, data were collected from 894 patients in four other hospitals. The prediction (PRE-DELIRIC) model contains 10 risk factors—age, APACHE-II score, admission group, coma, infection, metabolic acidosis, use of sedatives and morphine, urea concentration, and urgent admission. The model had an area under the receiver operating characteristics curve of 0.87 (95% confidence interval 0.85 to 0.89) and 0.86 after bootstrapping. Temporal validation and external validation resulted in areas under the curve of 0.89 (0.86 to 0.92) and 0.84 (0.82 to 0.87). The pooled area under the receiver operating characteristics curve (n=3056) was 0.85 (0.84 to 0.87). The area under the curve for nurses’ and physicians’ predictions (n=124) was significantly lower at 0.59 (0.49 to 0.70) for both. Conclusion The PRE-DELIRIC model for intensive care patients consists of 10 risk factors that are readily available within 24 hours after intensive care admission and has a high predictive value. Clinical prediction by nurses and physicians performed significantly worse. The model allows for early prediction of delirium and initiation of preventive measures. Trial registration Clinical trials NCT00604773 (development study) and NCT00961389 (validation study).

Delirium in critically ill patients: Impact on long-term health-related quality of life and cognitive functioning.

Objective:To examine the impact of delirium during intensive care unit stay on long-term health-related quality of life and cognitive function in intensive care unit survivors. Design:Prospective 18-month follow-up study. Setting:Four intensive care units of a university hospital. Patients:A median of 18 months after intensive care discharge, questionnaires were sent to 1,292 intensive care survivors with (n = 272) and without (n = 1020) delirium during their intensive care stay. Measurements and Main Results:The Short Form-36v1, checklist individual strength-fatigue, and cognitive failure questionnaire were used. Covariance analysis was performed to adjust for relevant covariates. Of the 915 responders, 171 patients were delirious during their intensive care stay (median age 65 [interquartile range 58–85], Acute Physiology and Chronic Health Evaluation II score 17 [interquartile range 14–20]), and 745 patients were not (median age 65 [interquartile range 57–72], Acute Physiology and Chronic Health Evaluation II score 13 [interquartile range 10–16]). After adjusting for covariates, no differences were found between delirium and nondelirium survivors on the Short Form-36 and checklist individual strength-fatigue. However, survivors who had suffered from delirium reported that they made significantly more social blunders, and their total cognitive failure questionnaire score was significantly higher, compared to survivors who had not been delirious. Survivors of a hypoactive delirium subtype performed significantly better on the domain mental health than mixed and hyperactive delirium patients. Duration of delirium was significantly correlated to problems with memory and names. Conclusions:Intensive care survivors with delirium during their intensive care unit stay had a similar adjusted health-related quality of life evaluation, but significantly more cognitive problems than those who did not suffer from delirium, even after adjusting for relevant covariates. In addition, the duration of delirium was related to long-term cognitive problems.

Faster wound healing with topical negative pressure therapy in difficult-to-heal wounds: a prospective randomized controlled trial.

Objective:A randomized clinical trial was conducted to determine the effectiveness and safety of topical negative pressure therapy in patients with difficult-to-heal wounds. Methods:A total of 24 patients were randomly assigned to either treatment with topical negative pressure therapy or treatment with conventional dressing therapy with sodium hypochlorite. The study end point was 50% reduction in wound volume. The maximum follow-up time was 6 weeks. Results:The median treatment time to 50% reduction of wound volume in the topical negative pressure group was 2.0 weeks (interquartile range = 1) versus 3.5 weeks (interquartile range = 1.5) in the sodium hypochlorite group (P < 0.001). The unadjusted hazard rate ratio for the time until 50% wound volume reduction was 0.123 (P < 0.001). After adjustment for relevant baseline characteristics in a Cox proportional hazards model treatment group, membership was found as the only and statistically significant indicator for the time to 50% wound volume reduction (hazard rate ratio of 0.117 [P < 0.001]). Subgroup analysis of spinal cord injured patients with severe pressure ulcers showed similar statistically significant results as in the total wound group. Conclusion:Topical negative pressure resulted in almost 2 times faster wound healing than treatment with sodium hypochlorite, and is safe to use in patients with difficult-to-heal wounds.

The effectiveness of topical negative pressure in the treatment of pressure ulcers: a literature review

The objective of the study was to gain insight into the effectiveness of vacuum-assisted closure (VAC) therapy or, more particularly, topical negative pressure (TNP) in the treatment of pressure ulcers. We carried out a systematic search in Medline, Embase and Cinahl for Randomized Clinical Trials (RCTs) involving topical negative pressure in pressure ulcers over the period 1992–2007. Five RCTs were included. Two studies dealt exclusively with pressure ulcers. No significant differences in wound healing were found in these studies. Three other studies (mixed etiology of wounds) did show significant differences in wound healing, in the decrease of wound treatment time, and in the decrease in number of bacteria. The quality of these studies, both in terms of methodology and otherwise, did not always match with the scientific standard. Moreover, these studies lacked subgroup analyses. The analyzed studies described positive effects of TNP, although both the control treatment and the end points varied in these studies. On the basis of the systematic assessment of these five RCTs, the conclusion is that TNP has not proven to be more effective than various control interventions. The differences between and within the studies in terms of control interventions, the differences in randomization and a number of weaknesses in the analyses do not allow a good comparison. The main recommendations for follow-up studies include: randomization of patients rather than of wounds, a homogeneous patient population, the use of a single well-defined and procedurally documented control intervention, and prior calculation of the random sample size.

Untangling ICU delirium: is establishing its prevention in high-risk patients the final frontier? Reply to van der Jagt et al

Dear Editor, We thank van der Jagt et al. [1] for their interest in our ICU delirium prediction model [2, 3]. We did not intend to imply that prediction of delirium, and the subsequent identification of highrisk groups, would make implementation easy. We acknowledge that changes in behavior are difficult to achieve, also for medical professionals, and that a multifaceted approach using different techniques and ways of feedback appears most successful. Nevertheless, we feel that identification of ICU patients with a high chance of developing delirium is essential for successful implementation of preventive measures. We have three reasons for this. First, use of a prediction model in future trials will facilitate comparability between groups and this will improve the validity and clinical acceptance of these trials. Second, clinicians could choose to focus on those patients with a high risk of developing delirium. We think that this will facilitate implementation, as no preventive measures, time, or money ‘are wasted’ on low-risk patients that do not need them. In preventive medicine in particular, identification of high-risk groups is paramount. Third, acceptance by family members as well as health-care workers to apply preventive measures is more likely if the chance to develop delirium in that particular patient is known. In our clinic we inform family members if the patient has a high risk for delirium, what the consequences can be, and how we try to prevent and eventually treat this. We do not agree with van der Jagt that because ‘no one has seen a patient die as a direct consequence of delirium’ this would make implementation more difficult. It is now clear that the presence of delirium is not merely an epiphenomenon of disease severity and therefore related to lower survival rates, but that there is clear attributable mortality [4]. Furthermore, if prevention is effective, the clinical observation of less patients suffering from delirium is likely to motivate caregivers to continue their preventive measures in addition to the effect of deleterious consequences of delirium that can be identified [5]. This might especially be true in patients suffering from hyperactive and mixed delirium, compared to hypoactive delirium, as the clinical picture is easier to recognize and more impressive. It remains true, however, that implementation of preventive measures during the complete ICU length of stay is likely more labor-intensive than implementation of other care bundles in ICU patients and we advocate the use of simultaneous techniques of implementation. Clinical intervention studies that demonstrate that prevention of delirium improves the outcome of critically ill patients would be most helpful for the implementation of measures to prevent delirium. We are currently conducting a randomized double-blind placebo-controlled trial in which haloperidol is tested to prevent delirium in ICU patients [6]. In 20 hospitals over 2,000 patients will be included, and the trial is powered to demonstrate an effect on patient survival. Finally, we found that over 20 ICU delirium prevention studies are currently listed in ClinicalTrials.gov, suggesting that more evidence to prevent delirium will become available in the coming years. References

Sustainability of clinical pathway guided care in cardiac surgery ICU patients; 9-years experience in over 7500 patients

Objective To determine trends over time regarding inclusion of post-operative cardiac surgery intensive care unit (ICU) patients in a clinical pathway (CP), and the association with clinical outcome. Design Retrospective cohort study. Setting ICU of an academic hospital. Participants All cardiac surgery patients operated between 2007 and 2015. Measures and Results A total of 7553 patients were operated. Three patient groups were identified: patients treated according to CP (n = 6567), patients excluded from the CP within the first 48 h (n = 633) and patients never included in CP (n = 353). Patients treated according to CP increased significantly over time from 74% to 95% and the median Log EuroSCORE (predicted mortality score) in this group increased significantly over time (P = 0.016). In-hospital length of stay (LOS) decreased in all groups, but significantly in CP group (P < 0.001). Overall, the in-hospital, and 1-year mortality decreased from 1.5 to 1.1% and 3.7 to 2.9%, respectively (both P < 0.05). Patients with a Log EuroSCORE >10 were more likely excluded from CP (P < 0.001), but, if included in CP, these patients had a significantly shorter Intensive Care stay and in-hospital stay compared to excluded patients with a Log EuroSCORE >10 (both P < 0.001). Conclusions The use of a CP for all post-operative cardiac surgery patients in the ICU is sustainable. While more complex patients were treated according to the CP, clinical outcome improved in the CP group.

Development and Validation of an Abbreviated Questionnaire to Easily Measure Cognitive Failure in ICU Survivors: A Multicenter Study

Objectives: To develop and validate an abbreviated version of the Cognitive Failure Questionnaire that can be used by patients as part of self-assessment to measure functional cognitive outcome in ICU survivors. Design: A retrospective multicenter observational study. Setting: The ICUs of two Dutch university hospitals. Patients: Adult ICU survivors. Interventions: None. Measurements and Main Results: Cognitive functioning was evaluated between 12 and 24 months after ICU discharge using the full 25-item Cognitive Failure Questionnaire (CFQ-25). Incomplete CFQ-25 questionnaires were excluded from analysis. Forward selection in a linear regression model was used in hospital A to assess which of the CFQ-25 items should be included to prevent a significant loss of correlation between an abbreviated and the full CFQ-25. Subsequently, the performance of an abbreviated Cognitive Failure Questionnaire was determined in hospital B using Pearson’s correlation. A Bland-Altman plot was used to examine whether the reduced-item outcome scores of an abbreviated Cognitive Failure Questionnaire were a replacement for the full CFQ-25 outcome scores. Among 1,934 ICU survivors, 1,737 were included, 819 in hospital A, 918 in hospital B. The Pearson’s correlation between the abbreviated 14-item Cognitive Failure Questionnaire (CFQ-14) and the CFQ-25 was 0.99. The mean of the difference scores was –0.26, and 95% of the difference scores fell within +5 and –5.5 on a 100-point maximum score. Conclusions: It is feasible to use the abbreviated CFQ-14 to measure self-reported cognitive failure in ICU survivors as this questionnaire has a similar performance as the full CFQ-25.

Delirium detection using relative delta power based on 1 minute single-channel EEG: a multicentre study

Background: Delirium is frequently unrecognised. EEG shows slower frequencies (i.e. below 4 Hz) during delirium, which might be useful in improving delirium recognition. We studied the discriminative performance of a brief single‐channel EEG recording for delirium detection in an independent cohort of patients. Methods: In this prospective, multicentre study, postoperative patients aged ≥60 yr were included (n=159). Before operation and during the first 3 postoperative days, patients underwent a 5‐min EEG recording, followed by a video‐recorded standardised cognitive assessment. Two or, in case of disagreement, three delirium experts classified each postoperative day based on the video and chart review. Relative delta power (1–4 Hz) was based on 1‐min artifact‐free EEG. The diagnostic value of the relative delta power was evaluated by the area under the receiver operating characteristic curve (AUROC), using the expert classification as the gold standard. Results: Experts classified 84 (23.3%) postoperative days as either delirium or possible delirium, and 276 (76.7%) non‐delirium days. The AUROC of the relative EEG delta power was 0.75 [95% confidence interval (CI) 0.69–0.82]. Exploratory analysis showed that relative power from 1 to 6 Hz had significantly higher AUROC (0.78, 95% CI 0.72–0.84, P=0.014). Conclusions: Delirium/possible delirium can be detected in older postoperative patients based on a single‐channel EEG recording that can be automatically analysed. This objective detection method with a continuous scale instead of a dichotomised outcome is a promising approach for routine detection of delirium. Clinical trial registration: NCT02404181.

MONITOR-IC study, a mixed methods prospective multicentre controlled cohort study assessing 5-year outcomes of ICU survivors and related healthcare costs: a study protocol

Introduction Due to advances in critical care medicine, more patients survive their critical illness. However, intensive care unit (ICU) survivors often experience long-term physical, cognitive and mental problems, summarised as post-intensive care syndrome (PICS), impacting their health-related quality of life (HRQoL). In what frequency PICS occurs, and to what extent this influences ICU survivors’ HRQoL, is mostly unknown. The aims of this study are therefore to study the: (1) 5-year patient outcomes, (2) predictors for PICS, (3) ratio between HRQoL of ICU survivors and healthcare-related costs, and (4) care and support needs. Methods The MONITOR-IC study is a multicentre prospective controlled cohort study, carried out in ICUs in four Dutch hospitals. Patients will be included between July 2016 and July 2021 and followed for 5 years. We estimated to include 12000 ICU patients. Outcomes are the HRQoL, physical, cognitive and mental symptoms, ICU survivors’ care and support needs, healthcare use and related costs. A control cohort of otherwise seriously ill patients will be assembled to compare long-term patient-reported outcomes. We will use a mixed methods design, including questionnaires, medical data from patient records, cost data from health insurance companies and interviews with patients and family members. Ethics and dissemination Insights from this study will be used to inform ICU patients and their family members about long-term consequences of ICU care, and to develop prediction and screening instruments to detect patients at risk for PICS. Subsequently, tailored interventions can be developed and implemented to prevent and mitigate long-term consequences. Additionally, insights into the ratio between HRQoL of ICU patients and related healthcare costs during 5 years after ICU admission can be used to discuss the added value of ICU care from a community perspective. The study has been approved by the research ethics committee of the Radboud University Medical Center (2016-2724). Clinical trial registration NCT03246334

Sufficient sleep quality easily measured: a multicenter centre study in dutch ICUS

Sleep is a fundamental need for recovery while a lack of good sleep is associated with adverse effects. ICU patients have an increased risk for disturbed sleep. Various sleeping questionnaires have been developed to assess the different aspects of sleep. The Richards Campbell Sleep Questionnaire (RCSQ) is one of the most commonly used sleep assessment tools for the ICU consisting of 5 questions on different aspects of sleep and reasons for poor sleep. However, it seems irrelevant to burden patients that state to have a good night sleep with the complete RCSQ. For clinical and developmental use it is useful to quantify sleep in a simple and effective manner. Therefore, the aim of our study was to investigate a simple sleeping numeric rating score; NRS sleep.