Pragmatic sedation strategies to prevent secondary brain injury in low-resource settings.

Traumatic brain injury is the alteration in brain function due to an external force. It is common and affects millions of people worldwide annually. The World Health Organization estimates that 90% of global deaths caused by injuries occur in low- and middle-income countries, with traumatic brain injury contributing up to half of these trauma-related deaths. Patients with traumatic brain injury in low- and middle-income countries have twice the odds of dying compared with their counterparts in high-income countries. Sedation is a key element of care in the management of traumatic brain injury, used for its neuroprotective effects and to prevent secondary brain injury. While sedatives have the potential to improve outcomes, they can be challenging to administer and have potentially dangerous complications. Sedation in low-resource settings should aim to be effective, safe, affordable and feasible. In this paper, we summarise the indications for sedation in traumatic brain injury, the choice of sedative drugs and the pragmatic management and monitoring of sedated traumatic brain injury patients in low-resource settings.

A Phase II Cluster-Crossover Randomized Trial of Fentanyl versus Morphine for Analgosedation in Mechanically Ventilated Patients.

Rationale: The continuous infusion of fentanyl or morphine is often prescribed to assist with analgesia and sedation (analgosedation) during mechanical ventilation. Objectives: To compare the effect of fentanyl versus morphine on patient-centered outcomes in ventilated patients. Methods: We conducted a cluster-randomized, cluster-crossover trial between July 2019 and August 2020 in two adult ICUs. We compared two continuous infusion regimens (fentanyl versus morphine). One ICU was randomized to the fentanyl-morphine sequence and the other to the morphine-fentanyl sequence. The primary outcome was the number of ventilator-free days at Day 28. Secondary outcomes included, among others, duration of mechanical ventilation in survivors and ICU-free days at Day 28. Measurements and Main Results: Via cluster allocation, we randomized 737 patients. Of these, 56 were excluded because of the opt-out consent process, leaving 681 (344 to fentanyl and 337 to morphine) for primary analysis (median [interquartile range] age, 59 [44-69] years). Median ventilator-free days at Day 28 were 26.1 (20.7-27.3) in the fentanyl versus 25.3 (19.1-27.2) in the morphine group (median difference, 0.79 [95% confidence interval, 0.31 to 1.28], P = 0.001). ICU-free days were greater (P < 0.001) and length of stay in the ICU for survivors shorter (P < 0.001) in the fentanyl group. All other secondary outcomes were not statistically different by treatment group. Conclusions: Among adult patients requiring mechanical ventilation, compared with morphine, fentanyl infusion significantly increased the median number of ventilator-free days at Day 28. The choice of opioid infusion agent may affect clinical outcomes and requires further investigation.

A plea for a unified approach to sedation in gastrointestinal endoscopy in Romania: results from a prospective multicentric trial.

Background. Adequate sedation is a prerequisite for quality endoscopic examination of the digestive tract. We aimed to evaluate the current practices and safety profile of sedation for gastrointestinal endoscopy in Romania and its impact on the technical success of the procedure and procedure-related adverse events. Methods. We conducted a prospective, multicentric, observational study including all patients undergoing digestive endoscopic procedures under various degrees of sedation. We collected data regarding the endoscopic procedure, type and degree of sedation, drug regimens, personnel in charge of sedation, and relevant patient related information. The main study outcome was the rate of sedation-related adverse events; secondary study outcomes included procedure-related adverse events and the impact of sedation on procedure success. Results. 1,043 consecutive endoscopic procedures from eight Romanian endoscopy units were included in our study. Sedation regimens were highly variable between participating centers, with 566 (54%) of procedures being performed under sedation provided by an anaesthesiologist. Sedation-related adverse events occurred in 40 cases (3.8%), most of them were mild respiratory and cardiovascular events and all reversed spontaneously. On multivariate analysis, male gender, procedure type (endoscopic ultrasound and endoscopic retrograde cholangiopancreatography) and deep sedation were risk factors for complications. The endoscopy unit, ASA status, age and type of sedative did not influence the complication rate. Conclusion. In conclusion, sedation for endoscopic procedures is generally safe, despite a high variability in sedation practices between centers in Romania. Establishing a national guideline on sedation for gastrointestinal endoscopy will ensure consistent and safe practice for these procedures.

Effect of dexmedetomidine on perioperative hemodynamics and organ protection in children with congenital heart disease: A randomized controlled trial.

BACKGROUND: This study aimed to investigate the effects of dexmedetomidine (Dex) on hemodynamics and organ protection in congenital heart disease (CHD) children who underwent open-heart surgery under cryogenic cardiopulmonary bypass. METHODS: Ninety children were randomly allocated to group C (0.9% saline 0.2 µg/kg/hour), group D1 (Dex 0.2 µg/kg/hour), and group D2 (Dex 0.4 µg/kg/hour) (n = 30 per group). All participants received fentanyl, propofol and 1% sevoflurane for anesthesia induction. Hemodynamic data were measured from T0 (before the induction) to T7 (30 minutes after extubation). The difference of arterial internal jugular vein bulbar oxygen difference and cerebral oxygen extraction ratio were calculated according to Fick formula. Enzyme-linked immunosorbent assay was performed to detect the serum myocardial, brain and kidney injury markers. The incidence of acute kidney injury (AKI) was calculated by serum creatinine level. Tracheal extubation time, postoperative pain score and emergence agitation score were also recorded. RESULTS: Compared with group C, group D1, and D2 exhibited reduction in hemodynamic parameters, myocardial and brain injury indicators, and tracheal extubation time. There were no significant differences in blood urea nitrogen and neutrophil gelatinase-associated lipocalin or incidence of AKI among the 3 groups. Besides, the incidence of tachycardia, nausea, vomiting and moderate agitation, and the FLACC scale in group D1 and D2 were lower than those in group C. Moreover, Dex 0.4 g/kg/hour could further reduce the dosage of fentanyl and dopamine compared with Dex 0.2 g/kg/hour. CONCLUSIONS: Dex anesthesia can effectively maintain hemodynamic stability and diminish organ injuries in CHD children.

A study comparing the effect of premedication with intravenous midazolam or dexmedetomidine on ketamine-fentanyl sedoanalgesia in burn patients: A randomized clinical trial.

INTRODUCTION: Dressing changes and wound care-debridement procedures often cause fear and anxiety in burn patients, as these processes are quite painful. In order to determine the best method for alleviating pain during these procedures, the current study compared the efficacy and safety of intravenous dexmedetomidine and midazolam for premedication prior to these painful burn care procedures. METHODS: This comparative and randomized study included patients who had a burn size of 1563%, were aged 1870 years, were diagnosed with the American Society of Anesthesiologists physical status (ASA I-II), and who underwent painful burn care procedures. Patients were intravenously administered either 1 mcg/kg dexmedetomidine (Group 1) or 0.03 mg/kg midazolam (Group 2) prior to the burn care procedure. Recorded at predetermined time points for each patient were heart rhythm (HR), mean arterial pressure (MAP), peripheral oxygen saturation (SpO2), standard bispectral index (BIS), and Ramsay Sedation Scale (RSS). RESULTS: In the dexmedetomidine group, HR and MAP measurements of patients ​​at the 3rd, 5th, and 10th mins during sedation were significantly lower than the baseline values (p < 0.05). A significant decrease in SpO2 was observed in both groups at the 10th min during sedation, but the decline was higher in the midazolam group (p < 0.05). BIS measurements of the patients in both groups were significantly lower at 10 min. during sedation and at 15th and 60th mins during the procedure (p < 0.05). However, there was no significant difference between the group (p > 0.05). The RSS scales of both groups in during the sedation were higher in the 3rd, 5th and 10th mins than the baseline values (p < 0.05), but there was no significant difference between the groups (p > 0.05). The RSS scales of groups in during the burn procedure were significantly higher at 15 th min than the 0 th values, while the RSS scales of both groups were significantly lower in the 45th and 60th mins (p < 0.05). CONCLUSION: Results of this study indicate that dexmedetomidine causes hemodynamic alterations while midazolam causes respiratory depression. However, these effects are not severe, and we conclude that both agents are safe and effective to ensure sedation prior to painful burn-care procedures.

The Use of Palliative Sedation to Treat Existential Suffering: A Scoping Review on Practices, Ethical Considerations, and Guidelines.

CONTEXT: Though palliative sedation has been recognized as an acceptable practice in Canada for many years now, there is a lack of clinical research and guidelines pertaining to its use as a treatment of existential refractory symptoms in the terminally ill. OBJECTIVES: This scoping review aimed to survey the literature surrounding palliative sedation and existential suffering and to inform research, policy, and practice. METHODS: To address the main research question: Is palliative sedation an acceptable intervention to treat existential refractory symptoms in adults aged 65 and older? a scoping review following Arksey and O'Malley's framework was performed, spanning electronic databases of the peer reviewed and grey literature. Articles were screened for inclusion, and a thematic content analysis allowed for a summary of key findings. RESULTS: Out of 427 search results, 71 full text articles were obtained, 20 of which were included. Out of these articles, four themes were identified as key findings. These included: (1) Ethical considerations; (2) The role of the health care provider; looking specifically at the impact on nurses; (3) The need for multidisciplinary care teams; and (4) Existential suffering's connection to religiosity and spirituality. CONCLUSION: Palliative sedation to treat existential refractory symptoms was labelled a controversial practice. A shortage of evidence-based resources limits the current literature's ability to inform policy and clinical practice. There is a need for both qualitative and quantitative multi-center research so health care professionals and regional-level institutions have firm roots to establish proper policy and practice.

Determination of blood dexmedetomidine in dried blood spots by LC-MS/MS to screen therapeutic levels in paediatric patients.

Dexmedetomidine is an imidazole derivative, with high affinity for α2 adrenergic receptors, used for sedation, analgesia and adjuvant anaesthesia. In this study, an analytical method for the quantification of dexmedetomidine in dried blood spots was developed, validated and applied. The drug was extracted from dried blood spot by liquid extraction; the separation was carried out by ultra high-resolution liquid chromatography in reverse phase coupled to tandem mass spectrometry method. An X Select cyano 5 µm HSS column (2.1 X 150 mm, Waters) and a mobile phase composed of 0.1% formic acid: acetonitrile [50:50 v/v], were used. The test was linear over the concentration range of 50 to 2000 pg/mL. The coefficients of variation for the intra and interday trials were less than 15%. The drug was stable under the conditions tested. The method was successfully applied for the quantification of 6 patients, aged 0 to 2 years, with classification ASA I, who underwent ambulatory surgeries, receiving a dose of 1 µg/Kg dexmedetomidine IV. The drug concentrations in the different sampling times were in the range of 76 to 868 pg/mL.

Application of sedation-agitation scale in conscious sedation before bronchoscopy in children.

This retrospective study investigated the application of the sedation-agitation scale (SAS) in pediatric bronchoscopy by observing its effects on sedative dosages and adverse reactions.Children who underwent sedation before bronchoscopy, during the period from January 2014 to June 2017, were divided into control and SAS groups. Patients in the control group were administered a single dose of 0.1 to 0.3 mg/kg midazolam, based on physicians' clinical experience. The initial dose of midazolam in the SAS group was 0.1 mg/kg, and was adjusted based on the SAS score, as evaluated by physicians. Between-group comparisons were made of midazolam dose; adverse reactions of midazolam, such as agitation, delirium, excessive sedation, and respiratory depression; operating time of bronchoscopy; and number of participants.No statistically significant differences in gender, age distribution, weight, or disease composition were observed between the groups. The midazolam dose, operating time, and number of participants at different ages were all lower in the SAS group than in the control group. Fewer adverse drug reactions, such as intraoperative agitation and delirium, were noted in the SAS group. Moreover, the overall number of participants was reduced, and the overall operating time was less than that in the control group.Application of SAS for assessment of sedation during pediatric bronchoscopy can guide individualized administration of midazolam, reduce midazolam dose while achieving an ideal sedative effect, reduce adverse reactions, and improve operator experience. Hence, its use should be promoted for pediatric patients undergoing bronchoscopy under local anesthesia and conscious sedation.

Prospective Observational Evaluation of Sedation and Pain Management Guideline Adherence Across New Jersey Intensive Care Units.

BACKGROUND: The practice guidelines for the management of pain, agitation, and delirium (PAD) from the Society of Critical Care Medicine shifted from primarily focusing on the treatment of anxiety in 2002 to the treatment of pain in 2013. OBJECTIVE: This prospective, observational, multicenter study aimed to assess the degree of practice adherence to the PAD guidelines for ventilated patients in New Jersey intensive care units (ICUs). METHODS: Pharmacist investigators at 8 centers designated 4 days at least 10 days apart to evaluate all patients on mechanical ventilation. The primary outcomes included adherence to 4 guideline recommendations: treatment of pain before sedation, use of nonnarcotic analgesic medications, use of nonbenzodiazepine sedative medications, and use of goal-directed sedation. RESULTS: Of 138 patients evaluated, 50% had a primary medical diagnosis (as opposed to surgical, cardiac, or neurological diagnosis), and the median Sequential Organ Failure Assessment (SOFA) score was 7. Pain was treated prior to administration of sedatives in 55.4% of subjects, with fentanyl being the primary analgesic used. In addition, 19% received no analgesia, and 11.5% received nonopioid analgesia. Sedative agents were administered to 87 subjects (48 nonbenzodiazepine and 39 benzodiazepine). Of those receiving benzodiazepines, 22 received intermittent bolus regimens and 16 received continuous infusions, of which 5 were for another indication besides sedation. Validated scales measuring the degree of sedation were completed at least once in 56 (81.6%) patients receiving sedatives. CONCLUSIONS: Current sedation practices suggest that integration of evidence-based PAD guidelines across New Jersey adult ICUs is inconsistent despite pharmacist involvement.

Does Equi-Minimum Alveolar Concentration Value Ensure Equivalent Analgesic or Hypnotic Potency?: A Comparison between Desflurane and Sevoflurane.

BACKGROUND: Minimum alveolar concentration (MAC) has traditionally been used to compare the potency of volatile anesthetics. However, as it reflects the spinal mechanism of immobility rather than the cerebral mechanism of analgesia and hypnosis, it is doubtful that equi-MAC connotes equivalent analgesic or hypnotic potency. The level of analgesia and hypnosis can be assessed using surgical pleth index and bispectral index (BIS) values, respectively. This study was designed to compare the surgical pleth index and BIS values produced by equi-MAC of desflurane and sevoflurane in patients undergoing single-agent volatile anesthesia. METHODS: Eighty-nine patients were randomly allocated to two groups receiving either desflurane (n = 44) or sevoflurane (n = 45). Anesthesia was only maintained with assigned volatile anesthetic of age-corrected 1.0 MAC. Surgical pleth index values as an analgesic estimate and BIS values as a hypnotic estimate were obtained under standard tetanic stimulation. RESULTS: Post-stimulation surgical pleth index values (mean ± SD), the primary outcome, were significantly lower for the desflurane group than those for the sevoflurane group (49 ± 10 vs. 64 ± 14, difference, 15 [95% CI, 10 to 20], P < 0.001). The desflurane group showed significantly lower poststimulation BIS values (median [interquartile range]) than the sevoflurane group (36 [31 to 41] vs. 41 [38 to 47], difference, 6 [95% CI, 2 to 9], P = 0.001). CONCLUSIONS: During a steady-state of 1.0 MAC, desflurane and sevoflurane did not cause similar surgical pleth index and BIS values under the standardized nociceptive stimulus. These findings suggest that equi-MAC of desflurane and sevoflurane may not ensure equivalent analgesic or hypnotic potency. VISUAL ABSTRACT: An online visual overview is available for this article at http://links.lww.com/ALN/B726.

Interprofessional Team's Perception of Care Delivery After Implementation of a Pediatric Pain and Sedation Protocol.

BACKGROUND: Pain and agitation are common experiences of patients in pediatric cardiac intensive care units. Variability in assessments by health care providers, communication, and treatment of pain and agitation creates challenges in management of pain and sedation. OBJECTIVES: To develop guidelines for assessment and treatment of pain, agitation, and delirium in the pediatric cardiac intensive unit in an academic children's hospital and to document the effects of implementation of the guidelines on the interprofessional team's perception of care delivery and team function. METHODS: Before and after implementation of the guidelines, interprofessional team members were surveyed about the members' perception of analgesia, sedation, and delirium management RESULTS: Members of the interprofessional team felt more comfortable with pain and sedation management after implementation of the guidelines. Team members reported improvements in team communication on patients' comfort. Members thought that important information was less likely to be lost during transfer of care. They also noted that the team carried out comfort management plans and used pharmacological and nonpharmacological therapies better after implementation of the guidelines than they did before implementation. CONCLUSIONS: Guidelines for pain and sedation management were associated with perceived improvements in team function and patient care by members of the interprofessional team.

Maintaining Interrater Agreement of Core Assessment Instruments in a Multisite Randomized Controlled Clinical Trial: The Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) Trial.

BACKGROUND: RESTORE (Randomized Evaluation of Sedation Titration for Respiratory Failure) was a cluster randomized clinical trial evaluating a sedation strategy in children 2 weeks to <18 years of age with acute respiratory failure supported on mechanical ventilation. A total of 31 U.S. pediatric intensive care units (PICUs) participated in the trial. Staff nurse rater agreement on measures used to assess a critical component of treatment fidelity was essential throughout the 4-year data collection period. OBJECTIVE: The purpose of the study is to describe the method of establishing and maintaining interrater agreement (IRA) of two core clinical assessment instruments over the course of the clinical trial. METHODS: IRA cycles were carried out at all control and intervention sites and included a minimum of five measurements of the State Behavioral Scale (SBS) and Withdrawal Assessment Tool-Version 1 (WAT-1). Glasgow Coma Scale scores were also obtained. PICUs demonstrating <80% agreement repeated their IRA cycle. Fleiss's kappa coefficient was used to assess IRA. RESULTS: Repeated IRA cycles were required for 8% of 226 SBS cycles and 2% of 222 WAT-1 cycles. Fleiss's kappa coefficients from more than 1,350 paired assessments were .86 for SBS and .92 for WAT-1, demonstrating strong agreement and similar to .91 for the Glasgow Coma Scale. There was no difference in Fleiss's kappa for any of the instruments based on unit size or timing of assessment (earlier or later in the study). For SBS scores, Fleiss's kappa was significantly different in larger and smaller PICUs (.82 vs. .92, p = .003); however, Fleiss's kappa for both groups indicated excellent agreement. CONCLUSION: Monitoring measurement reliability is an essential step in ensuring treatment fidelity and, thus, the validity of study results. Standardization on the use of these core assessment instruments among participating sites was achieved and maintained throughout the trial.

FDA Anesthesia Warning for Pregnant Women, Children.

ACOG, AAP, and others express concerns.

Evaluating Patient-Centered Outcomes in Clinical Trials of Procedural Sedation, Part 1 Efficacy: Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations.

The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership with the US Food and Drug Administration, convened a meeting of sedation experts from a variety of clinical specialties and research backgrounds with the objective of developing recommendations for procedural sedation research. Four core outcome domains were recommended for consideration in sedation clinical trials: (1) safety, (2) efficacy, (3) patient-centered and/or family-centered outcomes, and (4) efficiency. This meeting identified core outcome measures within the efficacy and patient-centered and/or family-centered domains. Safety will be addressed in a subsequent meeting, and efficiency will not be addressed at this time. These measures encompass depth and levels of sedation, proceduralist and patient satisfaction, patient recall, and degree of pain experienced. Consistent use of the recommended outcome measures will facilitate the comprehensive reporting across sedation trials, along with meaningful comparisons among studies and interventions in systematic reviews and meta-analyses.

Quality and clinical supply considerations of Paediatric Investigation Plans for IV preparations-A case study with the FP7 CloSed project.

A Paediatric Investigation Plan (PIP) is a development plan that aims to ensure that sufficient data are obtained through studies in paediatrics to support the generation of marketing authorisation of medicines for children. This paper highlights some practical considerations and challenges with respect to PIP submissions and paediatric clinical trials during the pharmaceutical development phase, using the FP7-funded Clonidine for Sedation of Paediatric Patients in the Intensive Care Unit (CloSed) project as a case study. Examples discussed include challenges and considerations regarding formulation development, blinding and randomisation, product labelling and shipment and clinical trial requirements versus requirements for marketing authorisation. A significant quantity of information is required for PIP submissions and it is hoped that future applicants may benefit from an insight into some critical considerations and challenges faced in the CloSed project.

The process of palliative sedation as viewed by physicians and nurses working in palliative care in Brazil.

OBJECTIVE: Our aim was to describe the process of palliative sedation from the point of view of physicians and nurses working in palliative care in Brazil. METHOD: Ours was a descriptive study conducted between May and December of 2011, with purposeful snowball sampling of 32 physicians and 29 nurses working in facilities in Brazil that have adopted the practice of palliative care. RESULTS: The symptoms prioritized for an indication of palliative sedation were dyspnea, delirium, and pain. Some 65.6% of respondents believed that the survival time of a patient in the final phase was not a determining factor for the indication of this measure, and that the patient, family, and healthcare team should participate in the decision-making process. For 42.6% of these professionals, the opinion of the family was the main barrier to an indication of this therapy. SIGNIFICANCE OF RESULTS: The opinion of the physicians and nurses who participated in this study converged with the principal national and international guidelines on palliative sedation. However, even though it is a therapy that has been adopted in palliative care, it remains a controversial practice.