2022 Society of Critical Care Medicine Clinical Practice Guidelines on Prevention and Management of Pain, Agitation, Neuromuscular Blockade, and Delirium in Critically Ill Pediatric Patients With Consideration of the ICU Environment and Early Mobility.

RATIONALE: A guideline that both evaluates current practice and provides recommendations to address sedation, pain, and delirium management with regard for neuromuscular blockade and withdrawal is not currently available. OBJECTIVE: To develop comprehensive clinical practice guidelines for critically ill infants and children, with specific attention to seven domains of care including pain, sedation/agitation, iatrogenic withdrawal, neuromuscular blockade, delirium, PICU environment, and early mobility. DESIGN: The Society of Critical Care Medicine Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility Guideline Taskforce was comprised of 29 national experts who collaborated from 2009 to 2021 via teleconference and/or e-mail at least monthly for planning, literature review, and guideline development, revision, and approval. The full taskforce gathered annually in-person during the Society of Critical Care Medicine Congress for progress reports and further strategizing with the final face-to-face meeting occurring in February 2020. Throughout this process, the Society of Critical Care Medicine standard operating procedures Manual for Guidelines development was adhered to. METHODS: Taskforce content experts separated into subgroups addressing pain/analgesia, sedation, tolerance/iatrogenic withdrawal, neuromuscular blockade, delirium, PICU environment (family presence and sleep hygiene), and early mobility. Subgroups created descriptive and actionable Population, Intervention, Comparison, and Outcome questions. An experienced medical information specialist developed search strategies to identify relevant literature between January 1990 and January 2020. Subgroups reviewed literature, determined quality of evidence, and formulated recommendations classified as "strong" with "we recommend" or "conditional" with "we suggest." Good practice statements were used when indirect evidence supported benefit with no or minimal risk. Evidence gaps were noted. Initial recommendations were reviewed by each subgroup and revised as deemed necessary prior to being disseminated for voting by the full taskforce. Individuals who had an overt or potential conflict of interest abstained from relevant votes. Expert opinion alone was not used in substitution for a lack of evidence. RESULTS: The Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility taskforce issued 44 recommendations (14 strong and 30 conditional) and five good practice statements. CONCLUSIONS: The current guidelines represent a comprehensive list of practical clinical recommendations for the assessment, prevention, and management of key aspects for the comprehensive critical care of infants and children. Main areas of focus included 1) need for the routine monitoring of pain, agitation, withdrawal, and delirium using validated tools, 2) enhanced use of protocolized sedation and analgesia, and 3) recognition of the importance of nonpharmacologic interventions for enhancing patient comfort and comprehensive care provision.

Prevalence of ICU Delirium in Postoperative Pediatric Cardiac Surgery Patients.

OBJECTIVES: The objective of this study was to determine the prevalence of ICU delirium in children less than 18 years old that underwent cardiac surgery within the last 30 days. The secondary aim of the study was to identify risk factors associated with ICU delirium in postoperative pediatric cardiac surgical patients. DESIGN: A 1-day, multicenter point-prevalence study of delirium in pediatric postoperative cardiac surgery patients. SETTING: Twenty-seven pediatric cardiac and general critical care units caring for postoperative pediatric cardiac surgery patients in North America. PATIENTS: All children less than 18 years old hospitalized in the cardiac critical care units at 06:00 on a randomly selected, study day. INTERVENTIONS: Eligible children were screened for delirium using the Cornell Assessment of Pediatric Delirium by the study team in collaboration with the bedside nurse. MEASUREMENT AND MAIN RESULTS: Overall, 181 patients were enrolled and 40% (n = 73) screened positive for delirium. There were no statistically significant differences in patient demographic information, severity of defect or surgical procedure, past medical history, or postoperative day between patients screening positive or negative for delirium. Our bivariate analysis found those patients screening positive had a longer duration of mechanical ventilation (12.8 vs 5.1 d; p = 0.02); required more vasoactive support (55% vs 26%; p = 0.0009); and had a higher number of invasive catheters (4 vs 3 catheters; p = 0.001). Delirium-positive patients received more total opioid exposure (1.80 vs 0.36 mg/kg/d of morphine equivalents; p < 0.001), did not have an ambulation or physical therapy schedule (p = 0.02), had not been out of bed in the previous 24 hours (p < 0.0002), and parents were not at the bedside at time of data collection (p = 0.008). In the mixed-effects logistic regression analysis of modifiable risk factors, the following variables were associated with a positive delirium screen: 1) pain score, per point increase (odds ratio, 1.3; 1.06-1.60); 2) total opioid exposure, per mg/kg/d increase (odds ratio, 1.35; 1.06-1.73); 3) SBS less than 0 (odds ratio, 4.01; 1.21-13.27); 4) pain medication or sedative administered in the previous 4 hours (odds ratio, 3.49; 1.32-9.28); 5) no progressive physical therapy or ambulation schedule in their medical record (odds ratio, 4.40; 1.41-13.68); and 6) parents not at bedside at time of data collection (odds ratio, 2.31; 1.01-5.31). CONCLUSIONS: We found delirium to be a common problem after cardiac surgery with several important modifiable risk factors.

Dexmedetomidine Use in Critically Ill Children With Acute Respiratory Failure.

OBJECTIVE: Care of critically ill children includes sedation but current therapies are suboptimal. To describe dexmedetomidine use in children supported on mechanical ventilation for acute respiratory failure. DESIGN: Secondary analysis of data from the Randomized Evaluation of Sedation Titration for Respiratory Failure clinical trial. SETTING: Thirty-one PICUs. PATIENTS: Data from 2,449 children; 2 weeks to 17 years old. INTERVENTIONS: Sedation practices were unrestrained in the usual care arm. Patients were categorized as receiving dexmedetomidine as a primary sedative, secondary sedative, periextubation agent, or never prescribed. Dexmedetomidine exposure and sedation and clinical profiles are described. MEASUREMENTS AND MAIN RESULTS: Of 1,224 usual care patients, 596 (49%) received dexmedetomidine. Dexmedetomidine as a primary sedative patients (n = 138; 11%) were less critically ill (Pediatric Risk of Mortality III-12 score median, 6 [interquartile range, 3-11]) and when compared with all other cohorts, experienced more episodic agitation. In the intervention group, time in sedation target improved from 28% to 50% within 1 day of initiating dexmedetomidine as a primary sedative. Dexmedetomidine as a secondary sedative usual care patients (n = 280; 23%) included more children with severe pediatric acute respiratory distress syndrome or organ failure. Dexmedetomidine as a secondary sedative patients experienced more inadequate pain (22% vs 11%) and sedation (31% vs 16%) events. Dexmedetomidine as a periextubation agent patients (n = 178; 15%) were those known to not tolerate an awake, intubated state and experienced a shorter ventilator weaning process (2.1 vs 2.3 d). CONCLUSIONS: Our data support the use of dexmedetomidine as a primary agent in low criticality patients offering the benefit of rapid achievement of targeted sedation levels. Dexmedetomidine as a secondary agent does not appear to add benefit. The use of dexmedetomidine to facilitate extubation in children intolerant of an awake, intubated state may abbreviate ventilator weaning. These data support a broader armamentarium of pediatric critical care sedation.

Structure, Process, and Culture Differences of Pediatric Trauma Centers Participating in an International Comparative Effectiveness Study of Children with Severe Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) is an important worldwide cause of death and disability for children. The Approaches and Decisions for Acute Pediatric TBI (ADAPT) Trial is an observational, cohort study to compare the effectiveness of six aspects of TBI care. Understanding the differences between clinical sites-including their structure, clinical processes, and culture differences-will be necessary to assess differences in outcome from the study and can inform the overall community regarding differences across academic centers. METHODS: We developed a survey and queried ADAPT site principal investigators with a focus on six domains: (i) hospital, (ii) pediatric intensive care unit (PICU), (iii) medical staff characteristics, (iv) quality of care, (v) medication safety, and (vi) safety culture. Summary statistics were used to describe differences between centers. RESULTS: ADAPT clinical sites that enrolled a subject within the first year (32 US-based, 11 international) were studied. A wide variation in site characteristics was observed in hospital and ICU characteristics, including an almost sevenfold range in ICU size (8-55 beds) and more than fivefold range of overall ICU admissions (537-2623). Nursing staffing (predominantly 1:1 or 1:2) and the presence of pharmacists within the ICU (79 %) were less variable, and most sites "strongly agreed" or "agreed" that Neurosurgery and Critical Care teams worked well together (81.4 %). However, a minority of sites (46 %) used an explicit protocol for treatment of children with severe TBI care. CONCLUSIONS: We found a variety of inter-center structure, process, and culture differences. These intrinsic differences between sites may begin to explain why interventional studies have failed to prove efficacy of experimental therapies. Understanding these differences may be an important factor in analyzing future ADAPT trial results and in determining best practices for pediatric severe TBI.

Clinician response time for positive blood culture results in a pediatric ICU.

INTRODUCTION: Positive blood cultures guide clinicians to prescribe specific therapy based on in vitro susceptibility. Delays in appropriate antibiotic therapy increase morbidity associated with positive blood culture. HYPOTHESIS: Time from clinician notification of positive blood culture to administration of targeted antimicrobial therapy should follow Surviving Sepsis guidelines. METHODS: Study setting was a 44 bed pediatric ICU. Data were extracted from the pharmacy database and the medical records of pediatric ICU patients with positive blood culture. Source, time blood culture was obtained, time of clinician notification of positive result, and administration time of first dose of new antimicrobial was captured. RESULTS: 174 positive blood cultures from 111 PICU patients were examined. Antimicrobials were changed after the positive culture in 51 (49%) patients. The new antibiotic was administered in an average of 6 h 35 min from clinician notification. CONCLUSIONS: We demonstrated a delay from clinician notification of positive culture to new antibiotic administration.

Protocolized sedation vs usual care in pediatric patients mechanically ventilated for acute respiratory failure: a randomized clinical trial.

IMPORTANCE: Protocolized sedation improves clinical outcomes in critically ill adults, but its effect in children is unknown. OBJECTIVE: To determine whether critically ill children managed with a nurse-implemented, goal-directed sedation protocol experience fewer days of mechanical ventilation than patients receiving usual care. DESIGN, SETTING, AND PARTICIPANTS: Cluster randomized trial conducted in 31 US pediatric intensive care units (PICUs). A total of 2449 children (mean age, 4.7 years; range, 2 weeks to 17 years) mechanically ventilated for acute respiratory failure were enrolled in 2009-2013 and followed up until 72 hours after opioids were discontinued, 28 days, or hospital discharge. INTERVENTION: Intervention PICUs (17 sites; n = 1225 patients) used a protocol that included targeted sedation, arousal assessments, extubation readiness testing, sedation adjustment every 8 hours, and sedation weaning. Control PICUs (14 sites; n = 1224 patients) managed sedation per usual care. MAIN OUTCOMES AND MEASURES: The primary outcome was duration of mechanical ventilation. Secondary outcomes included time to recovery from acute respiratory failure, duration of weaning from mechanical ventilation, neurological testing, PICU and hospital lengths of stay, in-hospital mortality, sedation-related adverse events, measures of sedative exposure (wakefulness, pain, and agitation), and occurrence of iatrogenic withdrawal. RESULTS: Duration of mechanical ventilation was not different between the 2 groups (intervention: median, 6.5 [IQR, 4.1-11.2] days; control: median, 6.5 [IQR, 3.7-12.1] days). Sedation-related adverse events including inadequate pain and sedation management, clinically significant iatrogenic withdrawal, and unplanned endotracheal tube/invasive line removal were not significantly different between the 2 groups. Intervention patients experienced more postextubation stridor (7% vs 4%; P = .03) and fewer stage 2 or worse immobility-related pressure ulcers (<1% vs 2%; P = .001). In exploratory analyses, intervention patients had fewer days of opioid administration (median, 9 [IQR, 5-15] days vs 10 [IQR, 4-21] days; P = .01), were exposed to fewer sedative classes (median, 2 [IQR, 2-3] classes vs 3 [IQR, 2-4] classes; P < .001), and were more often awake and calm while intubated (median, 86% [IQR, 67%-100%] of days vs 75% [IQR, 50%-100%] of days; P = .004) than control patients, respectively; however, intervention patients had more days with any report of a pain score ≥ 4 (median, 50% [IQR, 27%-67%] of days vs 23% [IQR, 0%-46%] of days; P < .001) and any report of agitation (median, 60% [IQR, 33%-80%] vs 40% [IQR, 13%-67%]; P = .003), respectively. CONCLUSIONS AND RELEVANCE: Among children undergoing mechanical ventilation for acute respiratory failure, the use of a sedation protocol compared with usual care did not reduce the duration of mechanical ventilation. Exploratory analyses of secondary outcomes suggest a complex relationship among wakefulness, pain, and agitation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00814099.

Defining sedation-related adverse events in the pediatric intensive care unit.

BACKGROUND: Clinical trials exploring optimal sedation management in critically ill pediatric patients are urgently needed to improve both short- and long-term outcomes. Concise operational definitions that define and provide best-available estimates of sedation-related adverse events (AE) in the pediatric population are fundamental to this line of inquiry. OBJECTIVES: To perform a multiphase systematic review of the literature to identify, define, and provide estimates of sedation-related AEs in the pediatric ICU setting for use in a multicenter clinical trial. METHODS: In Phase One, we identified and operationally defined the AE. OVID-MEDLINE and CINAHL databases were searched from January 1998 to January 2012. Key terms included sedation, intensive and critical care. We limited our search to data-based clinical trials from neonatal to adult age. In Phase Two, we replicated the search strategy for all AEs and identified pediatric-specific AE rates. RESULTS: We reviewed 20 articles identifying sedation-related adverse events and 64 articles on the pediatric-specific sedation-related AE. A total of eleven sedation-related AEs were identified, operationally defined and estimated pediatric event rates were derived. AEs included: inadequate sedation management, inadequate pain management, clinically significant iatrogenic withdrawal, unplanned endotracheal tube extubation, post-extubation stridor with chest-wall retractions at rest, extubation failure, unplanned removal of invasive tubes, ventilator-associated pneumonia, catheter-associated bloodstream infection, Stage II+ pressure ulcers and new tracheostomy. CONCLUSIONS: Concise operational definitions that defined and provided best-available event rates of sedation-related AEs in the pediatric population are presented. Uniform reporting of adverse events will improve subject and patient safety.

Prospective evaluation of sedation-related adverse events in pediatric patients ventilated for acute respiratory failure.

OBJECTIVES: Sedation-related adverse events in critically ill pediatric patients lack reproducible operational definitions and reference standards. Understanding these adverse events is essential to improving the quality of patient care and for developing prevention strategies in critically ill children. The purpose of this study was to test operational definitions and estimate the rate and site-to-site heterogeneity of sedation-related adverse events. DESIGN: Prospective cohort study. SETTING: Twenty-two pediatric intensive care units in the United States enrolling baseline patients into a prerandomization phase of a multicenter trial on sedation management. PATIENTS: Pediatric patients intubated and mechanically ventilated for acute respiratory failure. DATA EXTRACTION: Analysis of adverse event data using consistent operational definitions from a Web-based data management system. MEASUREMENTS AND MAIN RESULTS: There were 594 sedation-related adverse events reported in 308 subjects, for a rate of 1.9 adverse events per subject and 16.6 adverse events per 100 pediatric intensive care unit days. Fifty-four percent of subjects had at least one adverse event. Seven (1%) adverse events were classified as severe, 347 (58%) as moderate, and 240 (40%) as mild. Agitation (30% of subjects, 41% of events) and pain (27% of subjects, 29% of events) were the most frequently reported events. Eight percent of subjects (n = 24) experienced 54 episodes of clinically significant iatrogenic withdrawal. Unplanned endotracheal tube extubation occurred at a rate of 0.82 per 100 ventilator days, and 32 subjects experienced postextubation stridor. Adverse events with moderate intraclass correlation coefficients included: Inadequate sedation management (intraclass correlation coefficient = 0.130), clinically significant iatrogenic withdrawal (intraclass correlation coefficient = 0.088), inadequate pain management (intraclass correlation coefficient = 0.080), and postextubation stridor (intraclass correlation coefficient = 0.078). CONCLUSIONS: Operational definitions for sedation-related adverse events were consistently applied across multiple pediatric intensive care units. Adverse event rates were different from what has been previously reported in single-center studies. Many adverse events have moderate intraclass correlation coefficients, signaling site-to-site heterogeneity.

Effect of an anonymous reporting system on near-miss and harmful medical error reporting in a pediatric intensive care unit.

Adverse event reporting is a key element for improving patient safety. This study describes a new voluntary, anonymous reporting system that facilitates reporting of near-miss and patient harm events and an assessment of patient harm by the bedside care provider in a pediatric intensive care unit. The results demonstrated the effectiveness of the Patient Safety Report as a method to capture near-miss and patient harm events.

Preventable harm occurring to critically ill children.

OBJECTIVE: To develop a trigger tool for identifying adverse events occurring in critically ill pediatric patients; to identify and characterize adverse events and preventable adverse events experienced by critically ill pediatric patients; and to characterize the patients who experience preventable adverse events. DESIGN: Retrospective chart review using a trigger tool. SETTING: Pediatric intensive care unit of a tertiary, university-affiliated pediatric hospital. PATIENTS: A systematic sample of 259 pediatric intensive care unit patients from a 1-yr period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured frequency of occurrence (0.19 preventable adverse events per patient-day), severity of harm (78% minor, 19% moderate, 3% serious, no deaths), and type of event (sedation, 22%; skin, 16%; medical device complication, 14%; pulmonary, 13%; and cardiovascular, 11%). Patients who experienced preventable adverse events were younger, had longer lengths of stay, and had higher illness burdens. Preventable adverse events occurred more frequently among surgical patients than medical patients. CONCLUSIONS: Preventable adverse events occurred fairly frequently in the pediatric intensive care unit, but serious harm was rare. Conditions that increased the likelihood of a preventable adverse event were a) need for sedation or pain control; b) relative immobility; and c) need for vascular devices, feeding tubes, or ventilators. Adverse event prevention strategies that focus on improving patient monitoring under increased-risk conditions and improving early detection and treatment of potential harm will likely be more effective than strategies aimed at general error prevention.

The safety culture in a children's hospital.

Efforts to improve patient safety require an understanding of organizational culture. In a survey of inpatient healthcare providers in a children's hospital, physician perceptions of teamwork were higher than those of all other staff (P < .001). Recognition of the impact of stress and fatigue was low, and job satisfaction was high for all groups. A majority of respondents did not feel rewarded for incident reporting. Information on hospital-level safety culture can lead to targeted system improvement.

Effect of prone positioning on clinical outcomes in children with acute lung injury: a randomized controlled trial.

CONTEXT: In uncontrolled clinical studies, prone positioning appeared to be safe and to improve oxygenation in pediatric patients with acute lung injury. However, the effect of prone positioning on clinical outcomes in children is not known. OBJECTIVE: To test the hypothesis that at the end of 28 days infants and children with acute lung injury treated with prone positioning would have more ventilator-free days than those treated with supine positioning. DESIGN, SETTING, AND PATIENTS: Multicenter, randomized, controlled clinical trial conducted from August 28, 2001, to April 23, 2004, of 102 pediatric patients from 7 US pediatric intensive care units aged 2 weeks to 18 years who were treated with supine vs prone positioning. Randomization was concealed and group assignment was not blinded. INTERVENTION: Patients were randomized to either supine or prone positioning within 48 hours of meeting acute lung injury criteria, with those patients in the prone group being positioned within 4 hours of randomization and remaining prone for 20 hours each day during the acute phase of their illness for a maximum of 7 days, after which they were positioned supine. Both groups were treated using lung protective ventilator and sedation protocols, extubation readiness testing, and hemodynamic, nutrition, and skin care guidelines. MAIN OUTCOME MEASURE: Ventilator-free days to day 28. RESULTS: The trial was stopped at the planned interim analysis on the basis of the prespecified futility stopping rule. There were no differences in the number of ventilator-free days between the 2 groups (mean [SD], 15.8 [8.5] supine vs 15.6 [8.6] prone; mean difference, -0.2 days; 95% CI, -3.6 to 3.2; P = .91). After controlling for age, Pediatric Risk of Mortality III score, direct vs indirect acute lung injury, and mode of mechanical ventilation at enrollment, the adjusted difference in ventilator-free days was 0.3 days (95% CI, -3.0 to 3.5; P = .87). There were no differences in the secondary end points, including proportion alive and ventilator-free on day 28 (P = .45), mortality from all causes (P>.99), the time to recovery of lung injury (P = .78), organ-failure-free days (P = .88), and cognitive impairment (P = .16) or overall functional health (P = .12) at hospital discharge or on day 28. CONCLUSION: Prone positioning does not significantly reduce ventilator-free days or improve other clinical outcomes in pediatric patients with acute lung injury.

Effect of red blood cell transfusion on oxygen consumption in the anemic pediatric patient.

OBJECTIVE: To compare oxygen consumption (Vo(2)) measured by indirect calorimetry before and after a packed red blood cell (PRBC) transfusion in patients with isovolemic anemia. DESIGN: Prospective, repeated-measures clinical study. SETTING: Outpatient pediatric hematology-oncology clinic. PATIENTS: A total of 17 pediatric hematology-oncology outpatients undergoing a PRBC transfusion for a hematocrit of <26%. INTERVENTIONS: Vo(2) was measured by indirect calorimetry before and after a PRBC transfusion. MEASUREMENTS AND MAIN RESULTS: Baseline hematocrit averaged 23% (15.5-25.7%), hemoglobin averaged 8.24 g/dL (5.2 g/dL-9.3 g/dL). Patients received an average of 10.3 mL/kg (2.8-17.5 mL/kg) of PRBC. After PRBC transfusion, all patients had an increase in Vo(2), with a mean increase of 35.09 mL x min(-1) x m(-2) (5-75 mL x min(-1) x m(-2)) or 19% (3.1-52%; p <.001). No significant correlation was found between the pretransfusion hematocrit or the volume of red blood cells administered and the change in Vo(2). No significant change was noted in systolic blood pressure or respiratory rate. There were 14 patients who had a decrease in heart rate after PRBC transfusion, and seven patients who demonstrated an increase in Vo(2) of <10% were compared with patients with a > or =10% change. No significant difference was found in age, height, weight, initial hematocrit, or volume of red blood cells transfused between these two groups. CONCLUSIONS: A significant increase in Vo(2) was noted after a red blood cell transfusion in pediatric patients with isovolemic anemia. These findings suggest that Vo(2) was dependent on the supply of oxygen in this subset of pediatric patients. Responding to increased oxygen delivery by increasing Vo(2) implies that these patients were functioning in a state of relative oxygen deficit and had made physiologic adaptive changes to function in this state.