The Agents Intervening against Delirium in the Intensive Care Unit Trial (AID-ICU trial): A detailed statistical analysis plan.

BACKGROUND: The AID-ICU trial aims to assess the benefits and harms of haloperidol for the treatment of delirium in acutely admitted, adult intensive care unit (ICU) patients. This paper describes the detailed statistical analysis plan for the primary publication of results from the AID-ICU trial. METHODS: The AID-ICU trial is an investigator-initiated, pragmatic, international, multicentre, randomized, blinded, parallel-group trial allocating 1000 adult ICU patients with manifest delirium 1:1 to haloperidol or placebo. The primary outcome measure is days alive and out of hospital within 90 days post-randomization. Secondary outcome measures are days alive without delirium or coma, serious adverse reactions (SARs) to haloperidol, use of escape medicine, days alive without mechanical ventilation, and mortality, health-related quality-of-life measures and cognitive function 1-year post-randomization. Statistical analysis will be conducted in accordance with the current pre-specified statistical analysis plan. One formal interim analysis will be performed. The primary outcome will be adjusted for stratification variables (site and delirium motor subtype) and compared between treatment groups using a likelihood ratio test described by Jensen et al A secondary analysis will be conducted with additional adjustment of the primary outcome for prognostic variables at baseline. The primary conclusion of the trial will be based on the intention-to-treat analysis of the primary outcome adjusted for stratification variables. CONCLUSION: The AID-ICU trial will provide important, high-quality data on the benefits and harms of treatment with haloperidol in acutely admitted, adult patients with manifest delirium in the ICU.

The effects of preoperative point-of-care focused cardiac ultrasound in high-risk patients: study protocol for a prospective randomised controlled trial.

INTRODUCTION: Perioperative mortality and morbidity remain substantial in acute surgery. Risk factors include known cardiovascular disease, but preoperative screening is insensitive to occult cardiopulmonary conditions. Focused cardiac ultrasound (FOCUS) can disclose both structural and functional cardiac disease and provides insight into the patient's haemodynamic status. This study aims to clarify whether preoperative FOCUS changes clinical outcomes in high-risk patients. METHODS: This is a multi-centre, randomised, controlled, prospective study including patients ≥ 65 years of age scheduled for acute/emergency abdominal- or orthopaedic surgery. A total of 800 patients will be randomised to ± application of preoperative FOCUS. The primary endpoint is the proportion of patients admitted to hospital > 10 days or death within 30 days of surgery. The secondary endpoints include changes in the anaesthesia approach facilitated by FOCUS, biomarkers of organ function and perioperative complications. CONCLUSIONS: The knowledge generated from this study may facilitate changes in the anaesthesia evaluation and decision process and, consequently, in the entire perioperative anaesthesia clinical practice. The study has the potential to reduce the risk of perioperative cardiopulmonary complications which directly implies improved patient outcome and reduced hospital costs. FUNDING: The Research Fund of the Department of Anaesthesiology, Randers Regional Hospital, The Central Denmark Region's Medical Research Fund and the Hospital of Southern Jutland. TRIAL REGISTRATION: NCT03501927.

Agents intervening against delirium in the intensive care unit (AID-ICU) - Protocol for a randomised placebo-controlled trial of haloperidol in patients with delirium in the ICU.

BACKGROUND: Delirium among patients in the intensive care unit (ICU) is a common condition associated with increased morbidity and mortality. Haloperidol is the most frequently used pharmacologic intervention, but its use is not supported by firm evidence. Therefore, we are conducting Agents Intervening against Delirium in the Intensive Care Unit (AID-ICU) trial to assess the benefits and harms of haloperidol for the treatment of ICU-acquired delirium. METHODS: AID-ICU is an investigator-initiated, pragmatic, international, randomised, blinded, parallel-group, trial allocating adult ICU patients with manifest delirium 1:1 to haloperidol or placebo. Trial participants will receive intravenous 2.5 mg haloperidol three times daily or matching placebo (isotonic saline 0.9%) if they are delirious. If needed, a maximum of 20 mg/daily haloperidol/placebo is given. An escape protocol, not including haloperidol, is part of the trial protocol. The primary outcome is days alive out of the hospital within 90 days post-randomisation. Secondary outcomes are number of days without delirium or coma, serious adverse reactions to haloperidol, usage of escape medication, number of days alive without mechanical ventilation; mortality, health-related quality-of-life and cognitive function at 1-year follow-up. A sample size of 1000 patients is required to detect a 7-day improvement or worsening of the mean days alive out of the hospital, type 1 error risk of 5% and power 90%. PERSPECTIVE: The AID-ICU trial is based on gold standard methodology applied to a large sample of clinically representative patients and will provide pivotal high-quality data on the benefits and harms of haloperidol for the treatment ICU-acquired delirium.

Reliability of the surgical Pleth index for assessment of postoperative pain: a pilot study.

BACKGROUND: Postoperative pain control is essential and may have a beneficial effect on postoperative outcome and morbidity. Analgesia quality is controlled using tools such as a Numerical Rating Scale (NRS). These tools require cooperation and often fail in the presence of reduced awareness. The Surgical Pleth index (SPI) has been introduced as a monitoring tool for intraoperative pain under general anaesthesia. OBJECTIVE: We investigated the correlation between SPI and pain intensity, analgesic consumption and fitness for discharge in the postanaesthesia care unit. DESIGN: An observational study. SETTING: The central postanaesthesia care unit of our tertiary care hospital. PATIENTS: Written informed consent was obtained from 100 patients scheduled for elective surgery under general anaesthesia. Patients below the age of 18 years and those with an abnormal cardiac rhythm were excluded from the study. INTERVENTION: Patients were interviewed every 10 min for 2 h. MAIN OUTCOME MEASURES: Pain intensity measured by NRS, discomfort and Aldrete and Post-Anaesthetic Discharge Scoring System (PADSS) scores were noted. SPI and total dose of opioids administered were recorded. RESULTS: A total of 1300 pain measurements were recorded; 482 (37%) reflected no or mild pain (NRS 0 to 3), 532 (41%) moderate pain (NRS 4 to 6) and 286 (22%) severe pain (NRS 7 to 10). Both NRS (r = 0.62, P < 0.001) and SPI (r = 0.38, P < 0.001) correlated significantly with total opioid consumption. SPI showed a moderate correlation with NRS (r = 0.49, P < 0.001). Receiver operating characteristic analysis showed moderate sensitivity and specificity for discrimination between low and moderate pain (NRS ≤3) (sensitivity 67%, specificity 69% for SPI ≤45), and between moderate and severe pain (NRS >6) (sensitivity 72%, specificity 72% for SPI ≥57). SPI and NRS showed weak negative correlations with Aldrete and PADSS scores. CONCLUSION: Sensitivity and specificity of SPI to discriminate between low, moderate and severe pain levels was moderate. Both NRS and SPI correlated significantly with total opioid consumption.

Correlation of surgical pleth index with stress hormones during propofol-remifentanil anaesthesia.

Eighty patients undergoing elective ear-nose-throat surgery were enrolled in the present study to investigate the relationship between surgical pleth index (SPI) and stress hormones (ACTH, cortisol, epinephrine, norepinephrine) during general anaesthesia which was induced and maintained with propofol and remifentanil using a target-controlled infusion. The study concluded that the SPI had moderate correlation to the stress hormones during general anaesthesia, but no correlation during consciousness. Furthermore, SPI values were able to predict ACTH values with high sensitivity and specificity.

A randomised, controlled crossover comparison of the C-MAC videolaryngoscope with direct laryngoscopy in 150 patients during routine induction of anaesthesia.

BACKGROUND: The C-MAC® (Karl Storz, Tuttlingen, Germany) has recently been introduced as a new device for videolaryngoscopy guided intubation. The purpose of the present study was to compare for the first time the C-MAC with conventional direct laryngoscopy in 150 patients during routine induction of anaesthesia. METHODS: After approval of the institutional review board and written informed consent, 150 patients (ASA I-III) with general anaesthesia were enrolled. Computer-based open crossover randomisation was used to determine the sequence of the three laryngoscopies: Conventional direct laryngoscopy (HEINE Macintosh classic, Herrsching, Germany; blade sizes 3 or 4; DL group), C-MAC size 3 (C-MAC3 group) and C-MAC size 4 (C-MAC4 group) videolaryngoscopy, respectively. After 50 patients, laryngoscopy technique in the C-MAC4 group was changed to the straight blade technique described by Miller (C-MAC4/SBT). RESULTS: Including all 150 patients (70 male, aged (median [range]) 53 [20-82] years, 80 [48-179] kg), there was no difference of glottic view between DL, C-MAC3, C-MAC4, and C-MAC4/SBT groups; however, worst glottic view (C/L 4) was only seen with DL, but not with C-MAC videolaryngoscopy. In the subgroup of patients that had suboptimal glottic view with DL (C/L≥2a; n = 24), glottic view was improved in the C-MAC4/SBT group; C/L class improved by three classes in 5 patients, by two classes in 2 patients, by one class in 8 patients, remained unchanged in 8 patients, or decreased by two classes in 1 patient. The median (range) time taken for tracheal intubation in the DL, C-MAC3, C-MAC4 and C-MAC4/SBT groups was 8 sec (2-91 sec; n = 44), 10 sec (2-60 sec; n = 37), 8 sec (5-80 sec; n = 18) and 12 sec (2-70 sec; n = 51), respectively. CONCLUSIONS: Combining the benefits of conventional direct laryngoscopy and videolaryngoscopy in one device, the C-MAC may serve as a standard intubation device for both routine airway management and educational purposes. However, in patients with suboptimal glottic view (C/L≥2a), the C-MAC size 4 with straight blade technique may reduce the number of C/L 3 or C/L 4 views, and therefore facilitate intubation. Further studies on patients with difficult airway should be performed to confirm these findings.

Comparison of surgical stress index-guided analgesia with standard clinical practice during routine general anesthesia: a pilot study.

BACKGROUND: Surgical stress index (SSI), a novel multivariate index, has recently been proven to react well to surgical nociceptive stimuli and analgesic drug concentration changes during general anesthesia. We investigated the feasibility of application of SSI for guidance of remifentanil administration during propofol-remifentanil anesthesia. METHODS: Eighty patients scheduled for elective ear-nose-throat surgery were randomized into two groups, SSI-guided analgesia group (SSI group) and standard practice analgesia group (control group). In both groups, anesthesia was maintained with a propofol target-controlled infusion and adjusted stepwise by 0.5 microg/ml to keep bispectral index values between 40 and 60. In the SSI group, the predicted effect-site concentration of remifentanil was adjusted stepwise by 1 ng/ml to keep SSI values between 20 and 50, whereas in the control group, predicted effect-site concentration of remifentanil was adjusted according to traditional inadequate analgesia criteria. Anesthetics consumption, recovery times, and incidence of unwanted events were recorded. RESULTS: Remifentanil consumption (average normalized infusion rate) was lower in the SSI group than in the control group (mean +/- SD, 9.5 +/- 3.8 microg . kg(-1) . h(-1) vs. 12.3 +/- 5.2 microg . kg(-1) . h(-1); P < 0.05). The number of unwanted events was less in the SSI group (84) than in the control group (556; P < 0.01). Recovery times were comparable between groups. No patient reported intraoperative recall. CONCLUSIONS: SSI-guided anesthesia resulted in lower remifentanil consumption, more stable hemodynamics, and a lower incidence of unwanted events.

Laryngeal tube S II, laryngeal tube S disposable, Fastrach laryngeal mask and Fastrach laryngeal mask disposable during elective surgery: a randomized controlled comparison between reusable and disposable supraglottic airway devices.

BACKGROUND AND OBJECTIVE: Analogue disposable devices of the laryngeal tube S II (LTS II) and the Fastrach laryngeal intubation mask (ILMA, Fastrach), namely the laryngeal tube disposable (LTS-D) and the Fastrach laryngeal intubation mask disposable (Fastrach-D), have recently been introduced. The purpose of this study was to compare each reusable device with the corresponding disposable one, during routine surgery. METHODS: After informed consent, 120 American Society of Anesthesiologists I-III patients scheduled for routine minor surgery were randomly allocated to the LTS II (n = 30), the LTS-D (n = 30), the Fastrach (n = 30) and the Fastrach-D (n = 30) groups, respectively. Overall insertion success rates, time to first sufficient ventilation (V(e)t > or = 200 ml), resulting airway leak pressures (ALPs), subjective assessment of handling as well as patient comfort were determined. RESULTS: Insertion success rates of the LTS II, LTS-D, Fastrach and Fastrach-D were 30/30, 29/30, 30/30 and 30/30, respectively. Time to successful insertion in the LTS II vs. the LTS-D group, as well as in the Fastrach vs. the Fastrach-D group, showed significant differences [median (min-max) s: 38 (13-187), 23 (9-108), P < 0,05; 27.5 (6-110), 16 (8-82), P < 0.05]. The highest ALP could be observed in the LTS-D group [median (min-max): 40 (16-40), P < 0.001 vs. all other devices] and the lowest ALP in the Fastrach-D group [median (min-max): 24.5 (12-40)]. ALP did not differ significantly in any group during variation of cuff volume by +/-20 ml. Subjective assessment of handling was significantly (P < 0.001) better in the LTS-D group than in the LTS II, Fastrach and Fastrach-D groups. CONCLUSION: LTS II, LTS-D, Fastrach and Fastrach-D were all suitable for routine airway management. The LTS-D showed the best properties in terms of airway sealing and handling.

The C-MAC videolaryngoscope: first experiences with a new device for videolaryngoscopy-guided intubation.

We studied the efficacy of the C-MAC (Karl Storz, Tuttlingen, Germany), a new portable videolaryngoscope, in 60 patients during routine induction of anesthesia. It was possible to insert the blade (Size 3) of the C-MAC and to get a view of the glottis on the first attempt in all patients. Tracheal intubation also was successful in all 60 patients; 52 patients were intubated on the first attempt, 6 on the second, and 2 on the third. In 8 patients (13%), a gum elastic bougie guide was required. A Cormack-Lehane Class 1 view of the glottis was seen in 30 patients without external manipulation and in 45 with external manipulation, Class 2a view in 22 without and 12 with, Class 2b in 2 without, and Class 3 in 2 without manipulation. The median time taken for tracheal intubation was 16 s (range, 6-58 s). In addition, we describe our experience with 3 patients in whom we had unexpected difficulty with direct laryngoscopy with a conventional Macintosh laryngoscope (Cormack-Lehane Class 3, 4, and 4, respectively). These patients' airways were successfully managed on the first attempt when using the C-MAC Size 4 blade (improvement to Cormack-Lehane Class 1, 2a, and 2b, respectively) in a modified manner by uploading the epiglottis, which is known as "straight blade technique."