Thomas Strøm

A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial

BACKGROUND Standard treatment of critically ill patients undergoing mechanical ventilation is continuous sedation. Daily interruption of sedation has a beneficial effect, and in the general intesive care unit of Odense University Hospital, Denmark, standard practice is a protocol of no sedation. We aimed to establish whether duration of mechanical ventilation could be reduced with a protocol of no sedation versus daily interruption of sedation. METHODS Of 428 patients assessed for eligibility, we enrolled 140 critically ill adult patients who were undergoing mechanical ventilation and were expected to need ventilation for more than 24 h. Patients were randomly assigned in a 1:1 ratio (unblinded) to receive: no sedation (n=70 patients); or sedation (20 mg/mL propofol for 48 h, 1 mg/mL midazolam thereafter) with daily interruption until awake (n=70, control group). Both groups were treated with bolus doses of morphine (2.5 or 5 mg). The primary outcome was the number of days without mechanical ventilation in a 28-day period, and we also recorded the length of stay in the intensive care unit (from admission to 28 days) and in hospital (from admission to 90 days). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00466492. FINDINGS 27 patients died or were successfully extubated within 48 h, and, as per our study design, were excluded from the study and statistical analysis. Patients receiving no sedation had significantly more days without ventilation (n=55; mean 13.8 days, SD 11.0) than did those receiving interrupted sedation (n=58; mean 9.6 days, SD 10.0; mean difference 4.2 days, 95% CI 0.3-8.1; p=0.0191). No sedation was also associated with a shorter stay in the intensive care unit (HR 1.86, 95% CI 1.05-3.23; p=0.0316), and, for the first 30 days studied, in hospital (3.57, 1.52-9.09; p=0.0039), than was interrupted sedation. No difference was recorded in the occurrences of accidental extubations, the need for CT or MRI brain scans, or ventilator-associated pneumonia. Agitated delirium was more frequent in the intervention group than in the control group (n=11, 20%vs n=4, 7%; p=0.0400). INTERPRETATION No sedation of critically ill patients receiving mechanical ventilation is associated with an increase in days without ventilation. A multicentre study is needed to establish whether this effect can be reproduced in other facilities. FUNDING Danish Society of Anesthesiology and Intensive Care Medicine, the Fund of Danielsen, the Fund of Kirsten Jensa la Cour, and the Fund of Holger og Ruth Hess.

Long-term psychological effects of a no-sedation protocol in critically ill patients.

IntroductionA protocol of no sedation has been shown to reduce the time patients receive mechanical ventilation and to reduce intensive care and total hospital length of stay. The long-term psychological effects of this strategy have not yet been described. The purpose of the study was to test whether a strategy of no sedation alters long-term psychological outcome compared with a standard strategy with sedation.MethodsDuring intensive care stay, 140 patients requiring mechanical ventilation were randomized to either no sedation or sedation with daily interruption of sedation. This study was done as a single-blinded cohort study. After discharge, patients were interviewed by a neuropsychologist assessing quality of life, depression, anxiety, and posttraumatic stress disorder.ResultsTwo years after randomization, 38 patients were eligible for interview, and 26 patients were interviewed (13 from each group). No difference was found with respect to quality of life (Medical Outcome Study, 36-item short-form health survey). Both mental and physical components were nonsignificant. The Beck depression index was low in both groups (one patient in intervention group versus three patients in the control group were depressed, p = 0.32). Evaluated with the Impact of Events Scale, both groups had low stress scores (one in the intervention group versus two in the control group had scores greater than 32; p = 0.50). State anxiety scores were also low (28 in the control group versus 30 in the intervention group, p = 0.58).ConclusionsOur data suggest that a protocol of no sedation applied to critically ill patients undergoing mechanical ventilation does not increase the risk of long-term psychological sequelae after intensive care compared with standard treatment with sedation.

Comfort and patient-centred care without excessive sedation: the eCASH concept

We propose an integrated and adaptable approach to improve patient care and clinical outcomes through analgesia and light sedation, initiated early during an episode of critical illness and as a priority of care. This strategy, which may be regarded as an evolution of the Pain, Agitation and Delirium guidelines, is conveyed in the mnemonic eCASH—early Comfort using Analgesia, minimal Sedatives and maximal Humane care. eCASH aims to establish optimal patient comfort with minimal sedation as the default presumption for intensive care unit (ICU) patients in the absence of recognised medical requirements for deeper sedation. Effective pain relief is the first priority for implementation of eCASH: we advocate flexible multimodal analgesia designed to minimise use of opioids. Sedation is secondary to pain relief and where possible should be based on agents that can be titrated to a prespecified target level that is subject to regular review and adjustment; routine use of benzodiazepines should be minimised. From the outset, the objective of sedation strategy is to eliminate the use of sedatives at the earliest medically justifiable opportunity. Effective analgesia and minimal sedation contribute to the larger aims of eCASH by facilitating promotion of sleep, early mobilization strategies and improved communication of patients with staff and relatives, all of which may be expected to assist rehabilitation and avoid isolation, confusion and possible long-term psychological complications of an ICU stay. eCASH represents a new paradigm for patient-centred care in the ICU. Some organizational challenges to the implementation of eCASH are identified.

Liberation From Mechanical Ventilation in Critically Ill Adults: An Official American College of Chest Physicians/American Thoracic Society Clinical Practice Guideline: Inspiratory Pressure Augmentation During Spontaneous Breathing Trials, Protocols Minimizing Sedation, and Noninvasive Ventilation Immediately After Extubation.

Background An update of evidence‐based guidelines concerning liberation from mechanical ventilation is needed as new evidence has become available. The American College of Chest Physicians (CHEST) and the American Thoracic Society (ATS) have collaborated to provide recommendations to clinicians concerning liberation from the ventilator. Methods Comprehensive evidence syntheses, including meta‐analyses, were performed to summarize all available evidence relevant to the guideline panel’s questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, and the results were summarized in evidence profiles. The evidence syntheses were discussed and recommendations developed and approved by a multidisciplinary committee of experts in mechanical ventilation. Results Recommendations for three population, intervention, comparator, outcome (PICO) questions concerning ventilator liberation are presented in this document. The guideline panel considered the balance of desirable (benefits) and undesirable (burdens, adverse effects, costs) consequences, quality of evidence, feasibility, and acceptability of various interventions with respect to the selected questions. Conditional (weak) recommendations were made to use inspiratory pressure augmentation in the initial spontaneous breathing trial (SBT) and to use protocols to minimize sedation for patients ventilated for more than 24 h. A strong recommendation was made to use preventive noninvasive ventilation (NIV) for high‐risk patients ventilated for more than 24 h immediately after extubation to improve selected outcomes. The recommendations were limited by the quality of the available evidence. Conclusions The guideline panel provided recommendations for inspiratory pressure augmentation during an initial SBT, protocols minimizing sedation, and preventative NIV, in relation to ventilator liberation.

Enoxaparin, effective dosage for intensive care patients: double-blinded, randomised clinical trial

IntroductionIntensive care unit (ICU) patients are predisposed to thromboembolism. Routine prophylactic anticoagulation is widely recommended. Low-molecular-weight heparins, such as enoxaparin, are increasingly used because of predictable pharmacokinetics. This study aims to determine the subcutaneous (SC) dose of enoxaparin that would give the best anti-factor Xa levels in ICU patients.MethodsThe 72 patients admitted to a mixed ICU at Odense University Hospital (OUH) in Denmark were randomised into four groups to receive 40, 50, 60, or 70 mg SC enoxaparin for a period of 24 hours. Anti-factor Xa activity (aFXa) was measured before, and at 4, 12, and 24 hours after administration. An AFXa level between 0.1 to 0.3 IU/ml was considered evidence of effective antithrombotic activity.ResultsMedian peak (4 hours after administration), aFXa levels increased significantly with an increase in enoxaparin dose, from 0.13 IU/ml at 40 mg, to 0.14 IU/ml at 50 mg, 0.27 IU/ml at 60 mg, and 0.29 IU/ml at 70 mg (P = 0.002). At 12 hours after administration, median aFXa levels were still within therapeutic range for those patients who received 60 mg (P = 0.02).ConclusionsOur study confirmed that a standard dose of 40 mg enoxaparin yielded subtherapeutic levels of aFXa in critically ill patients. Higher doses resulted in better peak aFXa levels, with a ceiling effect observed at 60 mg. The present study seems to suggest inadequate dosage as one of the possible mechanisms for the higher failure rate of enoxaparin in ICU patients.Trial RegistrationISRCTN03037804

An Official American Thoracic Society/American College of Chest Physicians Clinical Practice Guideline: Liberation from Mechanical Ventilation in Critically Ill Adults. Rehabilitation Protocols, Ventilator Liberation Protocols, and Cuff Leak Tests

Background: Interventions that lead to earlier liberation from mechanical ventilation can improve patient outcomes. This guideline, a collaborative effort between the American Thoracic Society and the American College of Chest Physicians, provides evidence‐based recommendations to optimize liberation from mechanical ventilation in critically ill adults. Methods: Two methodologists performed evidence syntheses to summarize available evidence relevant to key questions about liberation from mechanical ventilation. The methodologists appraised the certainty in the evidence (i.e., the quality of evidence) using the Grading of Recommendations, Assessment, Development, and Evaluation approach and summarized the results in evidence profiles. The guideline panel then formulated recommendations after considering the balance of desirable consequences (benefits) versus undesirable consequences (burdens, adverse effects, and costs), the certainty in the evidence, and the feasibility and acceptability of various interventions. Recommendations were rated as strong or conditional. Results: The guideline panel made four conditional recommendations related to rehabilitation protocols, ventilator liberation protocols, and cuff leak tests. The recommendations were for acutely hospitalized adults mechanically ventilated for more than 24 hours to receive protocolized rehabilitation directed toward early mobilization, be managed with a ventilator liberation protocol, be assessed with a cuff leak test if they meet extubation criteria but are deemed high risk for postextubation stridor, and be administered systemic steroids for at least 4 hours before extubation if they fail the cuff leak test. Conclusions: The American Thoracic Society/American College of Chest Physicians recommendations are intended to support healthcare professionals in their decisions related to liberating critically ill adults from mechanical ventilation.

Official executive summary of an American Thoracic Society/American College of Chest Physicians clinical practice guideline: Liberation from mechanical ventilation in critically ill adults

Background: This clinical practice guideline addresses six questions related to liberation from mechanical ventilation in critically ill adults. It is the result of a collaborative effort between the American Thoracic Society and the American College of Chest Physicians. Methods: A multidisciplinary panel posed six clinical questions in a Population, Intervention, Comparator, and Outcomes format. A comprehensive literature search and evidence synthesis was performed for each question, which included appraising the certainty in the evidence (i.e., the quality of evidence) using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The Evidence‐to‐Decision framework was applied to each question, requiring the panel to evaluate and weigh the importance of the problem, the confidence in the evidence, the certainty about how much the public values the main outcomes, the magnitude and balance of desirable and undesirable outcomes, the resources and costs associated with the intervention, the impact on health disparities, and the acceptability and feasibility of the intervention. Results: Evidence‐based recommendations were formulated and graded initially by subcommittees and then modified after full‐panel discussions. The recommendations were confirmed by confidential electronic voting; approval required that at least 80% of the panel members agree with the recommendation. Conclusions: The panel provides recommendations regarding liberation from mechanical ventilation. The details regarding the evidence and rationale for each recommendation are presented in the American Journal of Respiratory and Critical Care Medicine and Chest.

The outcome of critical illness in decompensated alcoholic liver cirrhosis

The mortality of patients suffering from acute decompensated liver disease treated in the intensive care unit (ICU) varies between 50% and 100%. Previously published data suggest that liver‐specific score systems are less accurate compared with the ICU‐specific scoring systems acute physiology and chronic health evaluation II (APACHE II) and simplified organ failure assessment (SOFA) in predicting outcome. We hypothesized that in a Scandinavian cohort of ICU patients, APACHE II, SOFA, and simplified acute physiology score (SAPS II) were superior to predict outcome compared with the Child–Pugh score.

Liberation From Mechanical Ventilation in Critically Ill Adults: Executive Summary of an Official American College of Chest Physicians/American Thoracic Society Clinical Practice Guideline

Background This clinical practice guideline addresses six questions related to liberation from mechanical ventilation in critically ill adults. It is the result of a collaborative effort between the American Thoracic Society (ATS) and the American College of Chest Physicians (CHEST). Methods A multidisciplinary panel posed six clinical questions in a population, intervention, comparator, outcomes (PICO) format. A comprehensive literature search and evidence synthesis was performed for each question, which included appraising the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The Evidence‐to‐Decision framework was applied to each question, requiring the panel to evaluate and weigh the importance of the problem, confidence in the evidence, certainty about how much the public values the main outcomes, magnitude and balance of desirable and undesirable outcomes, resources and costs associated with the intervention, impact on health disparities, and acceptability and feasibility of the intervention. Results Evidence‐based recommendations were formulated and graded initially by subcommittees and then modified following full panel discussions. The recommendations were confirmed by confidential electronic voting; approval required that at least 80% of the panel members agree with the recommendation. Conclusions The panel provides recommendations regarding liberation from mechanical ventilation. The details regarding the evidence and rationale for each recommendation are presented in the American Journal of Respiratory and Critical Care Medicine and CHEST.

Non-sedation versus sedation with a daily wake-up trial in critically ill patients receiving mechanical ventilation (NONSEDA Trial) : study protocol for a randomised controlled trial

BackgroundThrough many years, the standard care has been to use continuous sedation of critically ill patients during mechanical ventilation. However, preliminary randomised clinical trials indicate that it is beneficial to reduce the sedation level. No randomised trial has been conducted comparing sedation with no sedation, a priori powered to have all-cause mortality as primary outcome.The objective is to assess the benefits and harms of non-sedation versus sedation with a daily wake-up trial in critically ill patients.Methods/DesignThe non-sedation (NONSEDA) trial is an investigator-initiated, randomised, clinical, parallel-group, multinational trial designed to include 700 patients from at least six ICUs in Denmark, Norway and Sweden.Inclusion criteria are mechanically ventilated patients with expected duration of mechanical ventilation >24 hours.Exclusion criteria are non-intubated patients, patients with severe head trauma, coma at admission or status epilepticus, patients treated with therapeutic hypothermia, patients with PaO2/FiO2 < 9 where sedation might be necessary to ensure sufficient oxygenation or place the patient in prone position.Experimental intervention is non-sedation supplemented with pain management during mechanical ventilation.Control intervention is sedation with a daily wake-up trial.The primary outcome will be all cause mortality at 90 days after randomization. Secondary outcomes will be: days until death throughout the total observation period; coma- and delirium-free days; highest RIFLE score; days until discharge from the intensive care unit (within 28 days); days until the participant is without mechanical ventilation (within 28 days); and proportion of patients with a major cardiovascular outcome. Explorative outcomes will be: all cause mortality at 28 days after randomisation; days until discharge from the intensive care unit; days until the participant is without mechanical ventilation; days until discharge from the hospital; organ failure.Trial size: we will include 700 participants (2 × 350) in order to detect or reject 25% relative risk reduction in mortality with a type I error risk of 5% and a type II error risk of 20% (power at 80%).DiscussionThe trial investigates potential benefits of non-sedation. This might have large impact on the future treatment of mechanically ventilated critically ill patients.Trial registerClinicalTrials.gov NCT0196768, 09.01.2014.