Epidural analgesia versus oral morphine for postoperative pain management following video-assisted thoracic surgery: A randomised, controlled, double-blind trial.

BACKGROUND: The use of thoracic epidural analgesia for postoperative pain management in video-assisted thoracic surgery (VATS) is controversial. Still, the evidence on omitting it in favour of systemic opioids is inconclusive, and studies are small and non-blinded. OBJECTIVE: We aimed to compare pain after VATS using epidural analgesia or enteral opioids for postoperative pain management. DESIGN/SETTING/PATIENTS/INTERVENTION: A randomised, double-blind, controlled trial at a Danish tertiary hospital. Adult patients scheduled for VATS were assigned to multimodal non-opioid baseline analgesia supplemented with either thoracic epidural analgesia (TE Group) or oral morphine (OM Group) for postoperative pain management. We recorded pain five times a day, both at rest and during activity, using the Numeric Rating Scale (NRS) and categorised it into "acceptable pain" or "unacceptable pain". Unacceptable pain was defined as NRS (at rest) ≥3 or NRS (with activity) ≥5 when supplementary analgesics were given. MAIN OUTCOME MEASURES: The primary outcomes were the proportions of patients experiencing "unacceptable pain" during the postoperative period and the use of intravenous "rescue" opioids. RESULTS: Of the 161 included patients, 146 received the allocated treatment and their data were analysed. At rest, 34% of patients in the TE Group and 64% of patients in the OM Group experienced unacceptable pain during the study period, a significant between-group difference of 30% ( P  < 0.0005). During activity these percentages were 32% of patients in the TE Group and 59% in the OM group, a difference of 27% ( P  < 0.005). The median intravenous rescue morphine consumption during the study period was 4.5 [interquartile range (IQR), 0-10.0] mg in the TE Group and 7.5 [0-19.0] mg in the OM Group ( P  < 0.005). CONCLUSION: Epidural analgesia provided better pain relief after VATS than oral morphine. The between-group difference in rescue intravenous morphine consumption was statistically significant but clinically irrelevant. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02359175).

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.).

A randomized, double-blind trial comparing the effect of two blood pressure targets on global brain metabolism after out-of-hospital cardiac arrest.

PURPOSE: This study aimed to assess the effect of different blood pressure levels on global cerebral metabolism in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA). METHODS: In a double-blinded trial, we randomly assigned 60 comatose patients following OHCA to low (63 mmHg) or high (77 mmHg) mean arterial blood pressure (MAP). The trial was a sub-study in the Blood Pressure and Oxygenation Targets after Out-of-Hospital Cardiac Arrest-trial (BOX). Global cerebral metabolism utilizing jugular bulb microdialysis (JBM) and cerebral oxygenation (rSO2) was monitored continuously for 96 h. The lactate-to-pyruvate (LP) ratio is a marker of cellular redox status and increases during deficient oxygen delivery (ischemia, hypoxia) and mitochondrial dysfunction. The primary outcome was to compare time-averaged means of cerebral energy metabolites between MAP groups during post-resuscitation care. Secondary outcomes included metabolic patterns of cerebral ischemia, rSO2, plasma neuron-specific enolase level at 48 h and neurological outcome at hospital discharge (cerebral performance category). RESULTS: We found a clear separation in MAP between the groups (15 mmHg, p < 0.001). Cerebral biochemical variables were not significantly different between MAP groups (LPR low MAP 19 (16-31) vs. high MAP 23 (16-33), p = 0.64). However, the LP ratio remained high (> 16) in both groups during the first 30 h. During the first 24 h, cerebral lactate > 2.5 mM, pyruvate levels > 110 µM, LP ratio > 30, and glycerol > 260 µM were highly predictive for poor neurological outcome and death with AUC 0.80. The median (IQR) rSO2 during the first 48 h was 69.5% (62.0-75.0%) in the low MAP group and 69.0% (61.3-75.5%) in the high MAP group, p = 0.16. CONCLUSIONS: Among comatose patients resuscitated from OHCA, targeting a higher MAP 180 min after ROSC did not significantly improve cerebral energy metabolism within 96 h of post-resuscitation care. Patients with a poor clinical outcome exhibited significantly worse biochemical patterns, probably illustrating that insufficient tissue oxygenation and recirculation during the initial hours after ROSC were essential factors determining neurological outcome.

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.

Postictal Encephalopathy After Status Epilepticus: Outcome and Risk Factors.

BACKGROUND: Postictal encephalopathy is well known after status epilepticus (SE), but its prognostic impact and triggers are unknown. Here, we aimed to establish risk factors for the development of postictal encephalopathy and to study its impact on survival after discharge. METHODS: This retrospective cohort study comprised adult patients diagnosed with first nonanoxic SE at Odense University Hospital between January 2008 and December 2017. Patients with ongoing SE at discharge or unknown treatment success were excluded. Postictal symptoms of encephalopathy were estimated retrospectively using the West Haven Criteria (WHC). WHC grade was determined for postictal day 1 to 14 or until the patient died or was discharged from the hospital. Cumulative postictal WHC during 14 days after SE-cessation was used to quantify postictal encephalopathy. Clinical characteristics, patient demographics, electroencephalographic and imaging features, and details on intensive care treatment were assessed from medical records. RESULTS: Of all eligible patients (n = 232), 198 (85.3%) had at least WHC grade 2 postictal encephalopathy that lasted for > 14 days in 24.5% of the surviving patients. WHC grade at discharge was strongly associated with poor long-term survival (p < 0.001). Postictal encephalopathy was not associated with nonconvulsive SE, postictal changes on magnetic resonance imaging, or distinct ictal patterns on electroencephalography. Although duration of SE and treatment in the intensive care unit showed an association with cumulative postictal WHC grade, they were not independently associated with the degree of encephalopathy when controlling for confounders. In a linear regression model, etiology, duration of sedation, age, and premorbid modified Rankin Scale were significant and consistent predictors for higher cumulative postictal WHC grade. Exploratory analyses showed an association of a cumulative midazolam dosage (mg/kg/h) with higher cumulative postictal WHC grade. DISCUSSION: In this cohort, postictal encephalopathy after SE was common and associated with poor long-term survival. Seizure characteristics were not independently associated with postictal encephalopathy; the underlying etiology, long (high-dose midazolam) sedation, high age, and poor premorbid condition were the major risk factors for its development.

Associations between clinical interventions and transcutaneous blood gas values in postoperative patients.

PURPOSE: Postoperative monitoring of circulation and respiration is pivotal to guide intervention strategies and ensure patient outcomes. Transcutaneous blood gas monitoring (TCM) may allow for noninvasive assessment of changes in cardiopulmonary function after surgery, including a more direct assessment of local micro-perfusion and metabolism. To form the basis for studies assessing the clinical impact of TCM complication detection and goal-directed-therapy, we examined the association between clinical interventions in the postoperative period and changes in transcutaneous blood gasses. METHODS: Two-hundred adult patients who have had major surgery were enrolled prospectively and monitored with transcutaneous blood gas measurements (oxygen (TcPO2) and carbon dioxide (TcPCO2)) for 2 h in the post anaesthesia care unit, with recording of all clinical interventions. The primary outcome was changes in TcPO2, secondarily TcPCO2, from 5 min before a clinical intervention versus 5 min after, analysed with paired t-test. RESULTS: Data from 190 patients with 686 interventions were analysed. During clinical interventions, a mean change in TcPO2 of 0.99 mmHg (95% CI-1.79-0.2, p = 0.015) and TcPCO2 of-0.67 mmHg (95% CI 0.36-0.98, p < 0.001) was detected. CONCLUSION: Clinical interventions resulted in significant changes in transcutaneous oxygen and carbon dioxide. These findings suggest future studies to assess the clinical value of changes in transcutaneous PO2 and PCO2 in a postoperative setting. TRIAL REGISTRY: Clinical trial number: NCT04735380. CLINICAL TRIAL REGISTRY: https://clinicaltrials.gov/ct2/show/NCT04735380.

Procedural Aspects of Epidural Catheter Placement: A Prospective Observational Study of 173 Epidural Catheter Insertions.

OBJECTIVE: The risks and benefits of epidural analgesia have been studied extensively, but information regarding many other aspects of epidural catheter insertion is limited. The authors aimed to add information regarding procedural pain, procedure duration, failure rates, and the effect of experience to the ongoing discussion on this procedure. DESIGN: A prospective observational study. SETTING: A Danish tertiary hospital. PARTICIPANTS: Patients scheduled to undergo video-assisted thoracic surgery. INTERVENTIONS: Epidural catheter insertion in 173 patients undergoing video-assisted thoracic surgery for lung cancer. MEASUREMENTS AND MAIN RESULTS: The authors recorded the time required for the epidural insertion procedure, the attempts used, insertion level, access use, patient position, placement technique used, and the designation of the physician placing the catheter. Furthermore, the authors asked the patients to evaluate the expected procedural pain, and after the procedure the authors asked them to evaluate the actual level of pain experienced. Six and 24 months after discharge, the authors examined persistent sequelae by using questionnaire assessments. The median procedure duration was 13 minutes, with 75% of the catheters placed within 22 minutes. Actual procedure-related pain (mean score [M] = 3.5, SD = 2.0) was significantly (p < 0.0001) less than that expected before the procedure (M = 4.9, SD = 2.0). The patients' expected pain, attempts required for successful catheter placement, and approach used to access the epidural space significantly affected the actual procedure-related pain (p = 0.001, p ≤ 0.003, and p = 0.023, respectively). Persistent pain and sensory disturbances were observed in 11% and 4% of the patients, respectively, after 6 months and in 6% and 4% of the patients, respectively, after 2 years. CONCLUSIONS: In this study, the authors examined several lesser-known aspects of epidural procedures. The use of epidural analgesia as part of the pain management plan after surgery requires a more complex evaluation instead of merely discussing the possibility of procedural infections, hematomas, or neurologic injuries. The procedure time, patients' expected and experienced pain related to the procedure, and the potential long-term side effects should be a part of the decision-making process.

Non-sedation-Does it improve health-related quality of life after critical illness? A 3-month follow-up sub-study of the NONSEDA trial.

BACKGROUND: Critical illness is associated with severely impaired health-related quality of life (HRQoL) for years following discharge. The NONSEDA trial was a multicenter randomized trial on non-sedation versus sedation with a daily wake-up trial in critically ill, mechanically ventilated patients in Scandinavia. The aim of this sub-study was to assess the effect of non-sedation on HRQoL and degree of independence in activities in daily living (ADL) 3 months post-ICU. METHODS: All survivors were asked to complete the Medical Outcomes Study Short-Form 36 questionnaire (SF-36) and the Barthel Index 3 months post-ICU. To limit missing data, reminders were sent. If unsuccessful, telephone interviews could be used. Outcomes were the level of HRQoL and ADL-function in each group. All outcomes were assessed blinded. RESULTS: Of the 700 patients included 412 survived to follow-up. A total of 344 survivors participated (82%). Baseline data were equal between the two groups. Mean SF-36 scores for the non-sedated vs sedated patients were as follows: Physical Function 45 vs 40, P = .69, Bodily Pain: 61 vs 52, P = .81, General Health: 50 vs 50, P = .84, Vitality: 42 vs 44, P = .85, Social Function: 75 vs 63, P = .85, Role Emotional: 58 vs 50, P = .82, Mental Health: 70 vs 70, P = .89, Role Physical: 25 vs 28, P = .32, Physical Component Score: 38 vs 37, P = .81, Mental Component Score: 48 vs 46, P = .94, Barthel Index: 20 vs 20, P = .74. CONCLUSION: Randomization to non-sedation neither improved nor impaired health-related quality of life or degree of independence in activities in daily living 3 months post-ICU discharge.

Effect of Nonsedation on Cognitive Function in Survivors of Critical Illness.

OBJECTIVES: Critical illness can cause severe cognitive impairments. The objective of this trial was to assess the effect of nonsedation versus sedation with a daily wake-up call during mechanical ventilation on cognitive function in adult survivors of critical illness. DESIGN: Single-center substudy of the multicenter, randomized Non-sedation Versus Sedation With a Daily Wake-up Trial in Critically Ill Patients Receiving Mechanical Ventilation trial. Three months after ICU-discharge participants were tested for cognitive function by a neuropsychologist. SETTING: Mixed 14-bed ICU in teaching hospital. PATIENTS: A total of 205 critically ill, orally intubated, and mechanically ventilated adults. INTERVENTIONS: Patients were randomized within the first 24 hours from intubation to either nonsedation with sufficient analgesia or light sedation with a daily wake-up call during mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: A total of 118 patients survived to follow-up and 89 participated (75%). The participating survivors in the two groups did not differ regarding baseline data or premorbid cognitive impairments. Sedated patients had received more sedatives, whereas doses of morphine and antipsychotics were equal. The primary outcome was that no significant difference was found in the number of patients with mild/moderate cognitive impairments (six nonsedated patients vs four sedated patients) or severe cognitive impairments (16 nonsedated patients vs 17 sedated patients; p = 0.71). Secondary outcomes were cognitive test scores, and no differences were found between the scores in nonsedated and sedated patients. Hypothetical worst case scenarios where all patients, who had not participated in follow-up assessment, were assumed to have severe cognitive impairments were analyzed, but still no difference between the groups was found. We found more patients with delirium in the sedated group (96% vs 69% of patients; p = 0.002) and increased duration of delirium in sedated patients (median 5 vs 1 d; p < 0.001). Delirium subtypes were equally distributed between the groups, with hypoactive delirium most frequent (61%), followed by mixed delirium (39%). CONCLUSIONS: Nonsedation did not affect cognitive function 3 months after ICU-discharge.

Low-Dose Naltrexone for the Treatment of Fibromyalgia: Investigation of Dose-Response Relationships.

OBJECTIVE: This study explores dose-response relationships when treating fibromyalgia with low-dose naltrexone. DESIGN: A single-blinded clinical trial was carried out using the "up-and-down" method. SUBJECTS: Subjects included women with a diagnosis of fibromyalgia aged 18-60 years who had been referred to treatment at a public pain clinic at a Danish university hospital. METHODS: The test doses were in the range 0.75-6 mg, and the dosing interval was 0.75 mg. The method was sequential and allowed predicting the dose effective in 50% (ED50) and 95% (ED95) of the subjects when the dose had shifted direction 10 times, and six pairs of "up-and-down" data were available. RESULTS: A total of 27 subjects were included in the study; two subjects were withdrawn. After inclusion of 25 evaluable subjects, the dose estimates were calculated as 3.88 mg for ED50 and 5.40 mg for ED95. As a secondary outcome, the effects on 10 common fibromyalgia symptoms were evaluated. A high interindividual variation was observed both in the symptom presentation at baseline and in which symptoms were reduced by low-dose naltrexone. CONCLUSIONS: This study is the first to explore dose-response relationships in the treatment of fibromyalgia with low-dose naltrexone. Future placebo-controlled randomized clinical trials are needed, and according to our findings, 4.5 mg, which has previously been used, seems to be a relevant test dose. We recommend that future studies include additional nonpain fibromyalgia symptoms as outcome measures.

Effect of non-sedation on post-traumatic stress and psychological health in survivors of critical illness-A substudy of the NONSEDA randomized trial.

BACKGROUND: Critical illness can cause post-traumatic stress and impaired mental health. The NONSEDA trial was a Scandinavian multicenter RCT, assessing non-sedation versus sedation with a daily wake-up call during mechanical ventilation in critically ill adults. The aim of this substudy was to assess the effect of non-sedation on post-traumatic stress and mental health. METHODS: This substudy is based on all participating patients from a single NONSEDA trial site (Kolding, Denmark). Patients were randomized to sedation or non-sedation within the first 24 hours of mechanical ventilation. Three months after ICU discharge survivors were examined by a neuropsychologist for post-traumatic stress, anxiety and depression, and filled out the SF-36 questionnaire regarding quality of life. RESULTS: The two groups of survivors were similar with regard to baseline characteristics, length of admission and mechanical ventilation. Sedated patients received more propofol and midazolam. Doses of morphine and haloperidole were equal. PRIMARY OUTCOME: the number of patients with post-traumatic stress disorder did not differ between groups (non-sedated: 2 patients vs sedated: 0, P = .23). SECONDARY OUTCOMES: there were no differences between groups in Beck Anxiety Index (median, non-sedated: 0 vs sedated: 0, P = .62), Beck Depression Index (median, non-sedated: 7 vs sedated: 4, P = .24), SF-36 mental component score (mean, non-sedated: 46.7 vs sedated: 47.5, P = .73) or number of patients with symptoms of post-traumatic stress (8 in both groups, P = .89). CONCLUSION: Levels of PTSD, anxiety and depression and quality of life regarding mental health were similar between the non-sedated and sedated group.

Urine neutrophil gelatinase-associated lipocalin and urine output as predictors of the successful discontinuation of continuous renal replacement therapy in critically ill patients with acute kidney injury.

BACKGROUND: Continuous renal replacement therapy (CCRT) is a frequently used modality for the support of intensive care patients with acute kidney injury (AKI). Nevertheless, there are no objective criteria for the discontinuation of CRRT. The purpose of this study was to investigate whether urine neutrophil gelatinase-associated lipocalin (uNGAL) alone or in combination with urine output could be used as a diagnostic test for renal function recovery in ICU patients on CRRT. METHODS: This was a single-centre prospective observational study including patients with acute kidney failure needing CRRT. Sixty-nine patients were enrolled, and 54 completed the study. Of the 54 patients, 22 recovered renal function (REC), defined as dialysis independency at 72 h from discontinuation, while 32 patients did not (NREC). Urine NGAL was measured at 0, 6, 12, and 24 h after CRRT discontinuation. The cumulated urine output was measured for 24 h prior to discontinuation and at 6, 12, and 24 h after discontinuation. Missing uNGAL values were calculated by interpolation. The Youden's index was used to calculate cut-off values in order to define uNGAL and urine output single variable and 2-variable diagnostic tests with the optimum prediction of successful CRRT discontinuation. RESULTS: Baseline characteristics at CRRT initiation were similar between groups. Compared to the NREC group, the REC group had significantly higher urine output (p < 0.0001) and lower uNGAL (p < 0.001) at all time points, except for uNGAL at 24 h (p < 0.24). The best uNGAL predictor for successful CRRT discontinuation was uNGAL at 6 h after discontinuation (predictive value 80%). The best single predictor was cumulated urine output 24 h before discontinuation (predictive value 85%). The combinations of uNGAL at 6 h (cut-off 1650 µg/L) with cumulated urine output 24 h prior to discontinuation (cut-off 210 ml) proved to be the superior tests (using either "or" or "and"), with predictive values of 93% (successful CRRT discontinuation) and 92% (dialysis dependency). CONCLUSIONS: With a predictive value of 93%, the combination of uNGAL at 6 h after and the cumulated urine output 24 h prior to CRRT cessation proved to be the best diagnostic test for successful CRRT discontinuation in ICU patients. CLINICAL TRIAL REGISTRATION: N/A.

Congenital diaphragmatic hernia presenting with symptoms within the first day of life; outcomes from a non-ECMO centre in Denmark.

BACKGROUND: Between 1998 and 2015, we report on the survival of congenital diaphragmatic hernia (CDH)-infants presenting with symptoms within the first 24 h of life, treated at Odense University Hospital (OUH), a tertiary referral non-extracorporeal membrane oxygenation (ECMO) hospital for paediatric surgery. METHODS: We performed a retrospective cohort study of prospectively identified CDH-infants at our centre. Data from medical records and critical information systems were obtained. Baseline data included mode of delivery and infant condition. Outcome data included 24-h, 28-day, and 1 year mortality rates and management data included intensive care treatment, length of stay in the intensive care unit, time of discharge from hospital, and surgical intervention. Descriptive analyses were performed for all variables. Survivors and non-survivors were compared for baseline and treatment data. RESULTS: Ninety-five infants were identified (44% female). Of these, 77% were left-sided hernias, 52% were diagnosed prenatally, and 6.4% had concurrent malformations. The 28-day mortality rate was 21.1%, and the 1 year mortality rate was 22.1%. Of the 21 non-survivors, nine died within the first 24 h, and 10 were sufficiently stabilised to undergo surgery. A statistically significant difference was observed between survivors and non-survivors regarding APGAR score at 1 and 5 min., prenatal diagnosis, body length at birth, and delivery at OUH. CONCLUSIONS: Our outcome results were comparable to published data from other centres, including centres using ECMO.

Atypical sleep in critically ill patients on mechanical ventilation is associated with increased mortality.

Sleep patterns in critically ill patients' polysomnographic sleep studies (PSG) are severely abnormal. PURPOSE: We aimed to investigate the association of atypical sleep patterns, micro-sleep phenomena (sleep spindles and K-complexes) and rapid eye movement (REM) sleep with intensive care unit (ICU), in-hospital and 90-day mortality in conscious critically ill patients on mechanical ventilation. METHOD: This was a prospective descriptive study. We analysed 52 PSGs recorded in conscious critically ill patients on mechanical ventilation. PSGs were scored according to standard classification when possible. Otherwise, modified classification proposed for scoring sleep in critically ill patients was used. The association of PSG findings with mortality was studied using logistic regression and Weibull model of survival analysis. RESULTS: The presence of atypical sleep patterns in accordance with modified sleep scoring classification was associated with higher odds for ICU mortality (odds ratio 11.63; p = 0.03). The absence of K-complexes was associated with higher odds for ICU mortality (odds ratio 11.63; p = 0.03), while the absence of sleep spindles was associated with higher odds for in-hospital (odds ratio 7.80; p = 0.02) and 90-day mortality (odds ratio 5.51; p = 0.02). Loss of sleep spindles was associated with higher mortality risk with cutoff point 90 days (hazard ratio 3.87; p = 0.03). CONCLUSIONS: The presence of atypical sleep and absence of normal PSG sleep characteristics in conscious critically ill patients on mechanical ventilation indicates involvement of sleep producing brain structures in the pathological process and is associated with poor outcome.

Negotiated mobilisation: An ethnographic exploration of nurse-patient interactions in an intensive care unit.

AIMS AND OBJECTIVES: To explore nurse-patient interactions in relation to the mobilisation of nonsedated and awake, mechanically ventilated patients in the intensive care unit. BACKGROUND: Lighter sedation has enabled the early mobilisation of mechanically ventilated patients, but little is known about the nurses' role and interaction with critically ill patients in relation to mobilisation. DESIGN AND METHODS: The study had a qualitative design using an ethnographic approach within the methodology of interpretive description. Data were generated in two intensive care units in Denmark, where a strategy of no sedation was applied. Participant observation was conducted during 58 nurse-patient interactions in relation to mobilisation between nurses (n = 44) and mechanically ventilated patients (n = 25). We conducted interviews with nurses (n = 16) and patients (n = 13) who had been mechanically ventilated for at least 3 days. The data were analysed using inductive, thematic analysis. The report of the study adhered to the COREQ checklist. FINDING: We identified three themes: "Diverging perspectives on mobilisation" showed that nurses had a long-term and treatment-oriented perspective on mobilisation, while patients had a short-term perspective and regarded mobilisation as overwhelming in their present situation. "Negotiation about mobilisation" demonstrated how patients actively negotiated the terms of mobilisation with the nurse. "Inducing hope through mobilisation" captured how nurses encouraged mobilisation by integrating aspects of the patient's daily life as a way to instil hope for the future. CONCLUSIONS: Exploring the nurse-patient interactions illustrated that mobilisation is more than physical activity. Mobilisation is accomplished through nurse-patient collaborations as a negotiated, complex and meaningful achievement, which is driven by the logic of care, leading to hope for the future. RELEVANCE TO CLINICAL PRACTICE: The study demonstrated the important role of nurses in achieving mobilisation in collaboration and through negotiation with mechanically ventilated patients in the intensive care unit.

Bedside Monitoring of Cerebral Energy State During Cardiac Surgery-A Novel Approach Utilizing Intravenous Microdialysis.

OBJECTIVES: This study investigated whether the lactate-to-pyruvate (LP) ratio obtained by microdialysis (MD) of the cerebral venous outflow reflected a derangement of global cerebral energy state during cardiopulmonary bypass (CPB). DESIGN: Interventional, prospective, randomized study. SETTING: Single-center, university teaching hospital. PARTICIPANTS: The study included 10 patients undergoing primary, elective coronary artery bypass grafting. INTERVENTIONS: Patients were randomized blindly to low mean arterial pressure (MAP) (40-60 mmHg; n = 5) or high MAP (60-80 mmHg; n = 5) during CPB. The MD catheters were positioned in a retrograde direction into the jugular bulb, and a reference catheter was inserted into the brachial artery. The correlations among LP ratio, MAP, data obtained from bifrontal near-infrared spectroscopy (NIRS), and postoperative neurologic outcome measures were assessed. MEASUREMENTS AND MAIN RESULTS: The correlated difference between pooled LP ratio (low and high MAP) of the jugular venous and the arterial blood was significant (LParterial 17 [15-20] v LPvenous 26 [23-27]; p = 0.0001). No cerebral desaturations (decrease in rSO2>20% from baseline) were observed in either group during CPB. In each group, 50% of the patients showed significant cognitive decline (mini-mental state examination, 3 points) 2 days after surgery. CONCLUSION: The LP ratio of cerebral venous blood increased significantly during CPB, indicating compromised cerebral oxidative metabolism. Conventional monitoring of rSO2 by NIRS did not show a corresponding decrease in cerebral oxygenation. As the patients exhibited decreased cognitive functions after CPB, increases in jugular venous LP ratio may be a sensitive indicator of impending cerebral damage.

Shoulder Pain After Thoracic Surgery: Type and Time Course, a Prospective Cohort Study.

OBJECTIVES: To study the time course of ipsilateral shoulder pain after thoracic surgery with respect to incidence, pain intensity, type of pain (referred versus musculoskeletal), and surgical approach. DESIGN: Prospective, observational cohort study. SETTING: Odense University Hospital, Denmark. PARTICIPANTS: Sixty patients for major lung resection. INTERVENTIONS: Postoperative observation of ipsilateral shoulder pain. MEASUREMENTS AND MAIN RESULTS: Postoperative numeric rating scale score of shoulder pain and thoracic pain and postoperative examination of the sites of shoulder pain for musculoskeletal involvement (muscle tenderness on palpation and movement) with follow-up 12 months after surgery. Clinically relevant pain was defined as a numeric rating scale score>3. Of the 60 patients included, 47 (78%) experienced ipsilateral shoulder pain, but only 25 (42%) reported clinically relevant shoulder pain. On postoperative day 4, 19 patients (32%) still suffered shoulder pain, but only 4 patients (7%) had clinically relevant pain. Four patients (8%) still suffered shoulder pain 12 months after surgery. In 26 patients (55%), the shoulder pain was classified as referred versus 21 patients (45%) who suffered shoulder pain of the musculoskeletal type. Shoulder pain of the musculoskeletal type was significantly more intense (p = 0.0008) than referred shoulder pain. CONCLUSION: Only a subset of patients has clinically relevant shoulder pain after postoperative day 2. Chronic shoulder pain is a minor problem after lobectomy and previously may have been overestimated. Ipsilateral shoulder pain of the musculoskeletal type is more intense than referred ipsilateral shoulder pain.

No-sedation during mechanical ventilation: impact on patient's consciousness, nursing workload and costs.

BACKGROUND: Evidence is growing that less or no-sedation is possible and beneficial for patients during mechanical ventilation. AIM: To investigate if there was a difference in patient consciousness and nursing workload comparing a group of patients receiving no-sedation with a group of sedated patients with daily wake up, and also to estimate economic consequences of a no-sedation strategy. DESIGN AND METHODS: Data were collected during a prospective trial of 140 mechanically ventilated patients randomized to either no-sedation or to sedation with daily wake up. From day 1 to 7 in the intensive care unit (ICU), patients were Richmond Agitation and Sedation Scale (RASS) scored, nursing workload was measured with the Nursing Care Recording System (NCR11) and nurse's self-assessment of workload was reported on a Numeric Rating Scale from 1 (low) to 10 (high). RESULTS: Patients from the no-sedation group had a median RASS score of -0·029 compared with -2 in the sedated group (P < 0·00001). The NCR11 scores were higher in the sedated group compared with the no-sedation group: 19·054 versus 17·05 (P = 0·00001). The nurses self-reported workload was the same in both groups (P = 0·085). Because of a shorter ICU stay and shorter hospital length of stay in the no-sedation group, we estimated that there will be no cost benefit with the use of sedation and a higher patient to nurse ratio. CONCLUSION: Patients receiving no-sedation were more awake with a RASS score close to zero, compared with patients receiving sedation and daily wake up. Nurses reported no difference in self-assessed workload between the no-sedation and sedated group of patients. RELEVANCE TO CLINICAL PRACTICE: Patients receiving no-sedation are more awake during their stay in ICU. There might be a potential economical saving with the use of a 1:1 nurse-patient ratio and no-sedation compared with sedation and a 1:2 nurse-patient ratio.