Subjective sleep assessment compared to polysomnography in mechanically ventilated critically ill ICU patients.

Sleep deprivation is expected in the intensive care unit (ICU) and is associated with delirium and increased mortality. Polysomnography (PSG) is the gold standard for sleep assessment, but practical issues limit the method. Hence, many ICUs worldwide use subjective sleep assessment (SSA) for sleep monitoring, but the agreement between SSA and PSG is unknown. The hypothesis was that the level of agreement between SSA and PSG was low and that total sleep time (TST) assessed with SSA would be overestimated compared to PSG in this existing cohort database. In this sub-analysis, 30 consecutive study participants underwent 15-h PSG recordings during two consecutive nights. The attending nurse performed an hourly subjective observer rating of sleep quantity during both nights, and the agreement between SSA and PSG was determined along with mean TST. Primary outcome: The level of agreement between SSA and PSG determined by Bland-Altman analysis. Secondary outcome: (1) The overall mean TST estimated by SSA compared to PSG in all study participants enrolled in the main study during both study nights, (2) TST for all study participants evaluated hourly during both study nights, (3) TST assessed with SSA compared to PSG in study participants sedated with dexmedetomidine during the second night and for study participants treated with placebo or non-sedation the first and second nights. The level of agreement between SSA and PSG was low. Mean TST estimated by SSA during the time interval 4.00 p.m. to 7.00 a.m. was 481 min (428;534, 95% CI) vs. PSG at 437 min (386;488, 95% CI) (p = .05). When sedated with dexmedetomidine, TST estimated using SSA was 650 min (571;729, 95% CI) versus PSG which was 588 min (531;645, 95% CI) (p = 0.56). For participants treated with placebo or non-sedation TST estimated with SSA was 397 min (343;450, 95% CI) versus PSG at 362 min (302;422, 95% CI) versus (p = 0.17). In mechanically ventilated critically ill ICU patients, the level of agreement between SSA and PSG was low, and there was a significant overestimation of mean TST. SSA should only be used under awareness that it is imprecise and overestimates TST.

Sleep quality and quantity determined by polysomnography in mechanically ventilated critically ill patients randomized to dexmedetomidine or placebo.

BACKGROUND: Abnormal sleep is commonly observed in the ICU and is associated with delirium and increased mortality. If sedation is necessary, it is often performed with gamma-aminobutyric acid agonists such as propofol or midazolam leading to an absence of restorative sleep. We aim to evaluate the effect of dexmedetomidine on sleep quality and quantity. METHODS: Thirty consecutive patients were included. The study was conducted as a double-blinded, randomized, placebo-controlled trial with two parallel groups: 20 patients were treated with dexmedetomidine, and 10 with placebo. Two 16 h of polysomnography recordings were done for each patient on two consecutive nights. Patients were randomized to dexmedetomidine or placebo after the first recording, thus providing a control recording for all patients. Dexmedetomidine was administered during the second recording (6 p.m.-6 a.m.). OBJECTIVE: To compare the effect of dexmedetomidine versus. placebo on sleep - quality and quantity. PRIMARY OUTCOME: Sleep quality, total sleep time (TST), Sleep efficiency (SE), and Rapid Eye Movement (REM) sleep determined by Polysomnography (PSG). SECONDARY OUTCOME: Delirium and daytime function determined by Confusion Assessment Method of the Intensive Care Unit and physical activity. Alertness and wakefulness were determined by RASS (Richmond Agitation and Sedation Scale). RESULTS: SE were increased in the dexmedetomidine group by; 37.6% (29.7;45.6 95% CI) versus 3.7% (-11.4;18.8 95% CI) (p < .001) and TST were prolonged by 271 min. (210;324 95% CI) versus 27 min. (-82;135 95% CI), (p < .001). No significant difference in REM sleep, delirium physical activity, or RASS score was found except for RASS night two. CONCLUSION: Total sleep time and sleep efficiency were significantly increased, without elimination of REM sleep, in mechanically ventilated ICU patients randomized to dexmedetomidine, when compared to a control PSG recording performed during non-sedation/standard care.

Dexmedetomidine and sleep quality in mechanically ventilated critically ill patients: study protocol for a randomised placebo-controlled trial.

INTRODUCTION: Sleep deprivation, which is a common complication in the intensive care unit (ICU), is associated with delirium and increased mortality. Sedation with gamma-aminobutyric acid agonists (propofol, benzodiazepine) results in significant disturbance of the sleep architecture. Dexmedetomidine is a lipophilic imidazole with an affinity for α2-adrenoceptors and it has sedative and analgesic properties. It has been reported to enhance sleep efficiency, thus sedate while preserving sleep architecture. METHODS AND ANALYSIS: Thirty consecutive patients are planned to be included, at the Department of Anesthesia and Intensive Care at the Hospital of Southwest Jutland, Denmark. The study is a double-blinded, randomised, controlled trial with two parallel groups (2:1 allocation ratio). Screening and inclusion will be done on day 1 from 8:00 to 16:00. Two 16 hours PSG (polysomnography) recording will be done starting at 16:00 on day 1 and day 2. Randomisation is performed if the first recording is of acceptable quality, otherwise the patient is excluded before randomisation. Dexmedetomidine/placebo will be administered during the second recording from 18:00 on day 2 to 6:00 on day 3. PRIMARY ENDPOINT: Improvement of total sleep time and sleep quality of clinical significance determined by PSG. SECONDARY ENDPOINTS: Sleep phases determined by PSG. Daytime function and delirium determined by Confusion Assessment Method-ICU. Alertness and wakefulness determined by Richmonde Agitation Sedation Scale. The objective is to compare the effect of dexmedetomidine versus placebo on sleep quality in critical ill mechanically ventilated patients. ETHICS AND DISSEMINATION: The trial investigate the potential benefit of dexmedetomidine on clinically relevant endpoints. If a beneficial effect is shown, this would have a large impact on future treatment of mechanically ventilated critically ill patients. Publication in peer-reviewed journal are plannedand the study has been approved by the National Committee on Health Research Ethics (ID:S-20180214). TRIAL REGISTRATION NUMBER: EudraCT (2017-001612-11DK) and Danish National Committee on Health Research Ethics (ID:S-20180214). The study related to pre-results.

Serum melatonin concentration in critically ill patients randomized to sedation or non-sedation.

BACKGROUND: Abolished circadian rhythm is associated with altered cognitive function, delirium, and as a result increased mortality in critically ill patients, especially in those who are mechanically ventilated. The causes are multifactorial, of which changes in circadian rhythmicity may play a role. Melatonin plays a crucial role as part of the circadian and sleep/wake cycle. Whether sedation effects circadian regulation is unknown. Hence, the objective of this study was to evaluate the melatonin concentration in critically ill patients randomized to sedation or non-sedation and to investigate the correlation with delirium. METHODS: All patients were included and randomized at the intensive care unit at the hospital of southwest Jutland, Denmark. Seventy-nine patients completed the study (41 sedated and 38 non-sedated). S-melatonin was measured 3 times per day, (03.00, 14.00, and 22.00), for 4 consecutive days in total, starting on the second day upon randomization/intubation. The study was conducted as a sub-study to the NON-SEDA study in which one hundred consecutive patients were randomized to sedation or non-sedation with a daily wake-up call (50 in each arm). PRIMARY OUTCOME: melatonin concentration in sedated vs. non-sedated patients (analyzed using linear regression). Secondary outcome: risk of developing delirium or non-medically induced (NMI) coma in sedated vs. non-sedated patients, assessed by CAM-ICU (Confusion Assessment Method for the Intensive Care Unit) analyzed using logistic regression. RESULTS: Melatonin concentration was suppressed in sedated patients compared to the non-sedated. All patients experienced an elevated peak melatonin level early on in the course of their critical illness (p = 0.01). The risk of delirium or coma (NMI) was significantly lower in the non-sedated group (OR 0.42 CI 0.27; 0.66 p < 0.0001). No significant relationship between delirium development and suppressed melatonin concentration was established in this study (OR 1.004 p = 0.29 95% CI 0.997; 1.010). CONCLUSION: Melatonin concentration was suppressed in sedated, critically ill patients, when compared to non-sedated controls and the frequency of delirium was elevated in sedated patients. Trail registration Clinicaltrials.gov (NCT01967680) on October 23, 2013.

Nonsedation or Light Sedation in Critically Ill, Mechanically Ventilated Patients.

BACKGROUND: In critically ill, mechanically ventilated patients, daily interruption of sedation has been shown to reduce the time on ventilation and the length of stay in the intensive care unit (ICU). Data on whether a plan of no sedation, as compared with a plan of light sedation, has an effect on mortality are lacking. METHODS: In a multicenter, randomized, controlled trial, we assigned, in a 1:1 ratio, mechanically ventilated ICU patients to a plan of no sedation (nonsedation group) or to a plan of light sedation (i.e., to a level at which the patient was arousable, defined as a score of -2 to -3 on the Richmond Agitation and Sedation Scale [RASS], on which scores range from -5 [unresponsive] to +4 [combative]) (sedation group) with daily interruption. The primary outcome was mortality at 90 days. Secondary outcomes were the number of major thromboembolic events, the number of days free from coma or delirium, acute kidney injury according to severity, the number of ICU-free days, and the number of ventilator-free days. Between-group differences were calculated as the value in the nonsedation group minus the value in the sedation group. RESULTS: A total of 710 patients underwent randomization, and 700 were included in the modified intention-to-treat analysis. The characteristics of the patients at baseline were similar in the two trial groups, except for the score on the Acute Physiology and Chronic Health Evaluation (APACHE) II, which was 1 point higher in the nonsedation group than in the sedation group, indicating a greater chance of in-hospital death. The mean RASS score in the nonsedation group increased from -1.3 on day 1 to -0.8 on day 7 and, in the sedation group, from -2.3 on day 1 to -1.8 on day 7. Mortality at 90 days was 42.4% in the nonsedation group and 37.0% in the sedated group (difference, 5.4 percentage points; 95% confidence interval [CI], -2.2 to 12.2; P = 0.65). The number of ICU-free days and of ventilator-free days did not differ significantly between the trial groups. The patients in the nonsedation group had a median of 27 days free from coma or delirium, and those in the sedation group had a median of 26 days free from coma or delirium. A major thromboembolic event occurred in 1 patient (0.3%) in the nonsedation group and in 10 patients (2.8%) in the sedation group (difference, -2.5 percentage points; 95% CI, -4.8 to -0.7 [unadjusted for multiple comparisons]). CONCLUSIONS: Among mechanically ventilated ICU patients, mortality at 90 days did not differ significantly between those assigned to a plan of no sedation and those assigned to a plan of light sedation with daily interruption. (Funded by the Danish Medical Research Council and others; NONSEDA ClinicalTrials.gov number, NCT01967680.).

In-hospital resuscitation evaluated by in situ simulation: a prospective simulation study.

BACKGROUND: Interruption in chest compressions during cardiopulmonary resuscitation can be characterized as no flow ratio (NFR) and the importance of minimizing these pauses in chest compression has been highlighted recently. Further, documentation of resuscitation performance has been reported to be insufficient and there is a lack of identification of important issues where future efforts might be beneficial. By implementing in situ simulation we created a model to evaluate resuscitation performance. The aims of the study were to evaluate the feasibility of the applied method, and to examine differences in the resuscitation performance between the first responders and the cardiac arrest team. METHODS: A prospective observational study of 16 unannounced simulated cardiopulmonary arrest scenarios was conducted. The participants of the study involved all health care personel on duty who responded to a cardiac arrest. We measured NFR and time to detection of initial rhythm on defibrillator and performed a comparison between the first responders and the cardiac arrest team. RESULTS: Data from 13 out of 16 simulations was used to evaluate the ability of generating resuscitation performance data in simulated cardiac arrest. The defibrillator arrived after median 214 seconds (180-254) and detected initial rhythm after median 311 seconds (283-349). A significant difference in no flow ratio (NFR) was observed between the first responders, median NFR 38% (32-46), and the resuscitation teams, median NFR 25% (19-29), p < 0.001. The difference was significant even after adjusting for pulse and rhythm check and shock delivery. CONCLUSION: The main finding of this study was a significant difference between the first responders and the cardiac arrest team with the latter performing more adequate cardiopulmonary resuscitation with regards to NFR. Future research should focus on the educational potential for in-situ simulation in terms of improving skills of hospital staff and patient outcome.

[Amoxicillin-induced hepatitis]. / Medikamentel hepatitis induceret af amoxicillin.

Amoxicillin with and without clavulanic acid is a widely used antibiotic in adults and children alike. The drug is used prophylactically as well as therapeutically. In Denmark, it has not been described that amoxicillin alone can lead to hepatitis. In literature often referenced by Danish physicians (medicin.dk and Lægemiddelkataloget), hepatotoxicity is not listed as a side effect. However, in the present case, a 61 year-old male who suffered a tick bite and was treated prophylactically with amoxicillin without clavulanic acid presented with pharmacologically induced hepatitis 20 days after treatment.