J. Mark Ansermino

Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model

BACKGROUND Pre-eclampsia is a leading cause of maternal deaths. These deaths mainly result from eclampsia, uncontrolled hypertension, or systemic inflammation. We developed and validated the fullPIERS model with the aim of identifying the risk of fatal or life-threatening complications in women with pre-eclampsia within 48 h of hospital admission for the disorder. METHODS We developed and internally validated the fullPIERS model in a prospective, multicentre study in women who were admitted to tertiary obstetric centres with pre-eclampsia or who developed pre-eclampsia after admission. The outcome of interest was maternal mortality or other serious complications of pre-eclampsia. Routinely reported and informative variables were included in a stepwise backward elimination regression model to predict the adverse maternal outcome. We assessed performance using the area under the curve (AUC) of the receiver operating characteristic (ROC). Standard bootstrapping techniques were used to assess potential overfitting. FINDINGS 261 of 2023 women with pre-eclampsia had adverse outcomes at any time after hospital admission (106 [5%] within 48 h of admission). Predictors of adverse maternal outcome included gestational age, chest pain or dyspnoea, oxygen saturation, platelet count, and creatinine and aspartate transaminase concentrations. The fullPIERS model predicted adverse maternal outcomes within 48 h of study eligibility (AUC ROC 0·88, 95% CI 0·84-0·92). There was no significant overfitting. fullPIERS performed well (AUC ROC >0·7) up to 7 days after eligibility. INTERPRETATION The fullPIERS model identifies women at increased risk of adverse outcomes up to 7 days before complications arise and can thereby modify direct patient care (eg, timing of delivery, place of care), improve the design of clinical trials, and inform biomedical investigations related to pre-eclampsia. FUNDING Canadian Institutes of Health Research; UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction; Preeclampsia Foundation; International Federation of Obstetricians and Gynecologists; Michael Smith Foundation for Health Research; and Child and Family Research Institute.

Consensus-Based Recommendations for Standardizing Terminology and Reporting Adverse Events for Emergency Department Procedural Sedation and Analgesia in Children

Children commonly require sedation and analgesia for procedures in the emergency department. Establishing accurate adverse event and complications rates from the available literature has been difficult because of the difficulty in aggregating results from previous studies that have used varied terminology to describe the same adverse events and outcomes. Further, serious adverse events occur infrequently, necessitating the study of large numbers of children to assess safety. These limitations prevent the establishment of a sufficiently large database on which evidence-based practice guidelines may be based. We assembled a panel of pediatric sedation researchers and experts to develop consensus-based recommendations for standardizing procedural sedation and analgesia terminology and reporting of adverse events. Our goal was to create a uniform reporting mechanism for future studies to facilitate the aggregation and comparison of results.

Predicting fluid responsiveness in children: a systematic review.

BACKGROUND: Administration of fluid to improve cardiac output is the mainstay of hemodynamic resuscitation. Not all patients respond to fluid therapy, and excessive fluid administration is harmful. Predicting fluid responsiveness can be challenging, particularly in children. Numerous hemodynamic variables have been proposed as predictors of fluid responsiveness. Dynamic variables based on the heart–lung interaction appear to be excellent predictors of fluid responsiveness in adults, but there is no consensus on their usefulness in children. METHODS: We systematically reviewed the current evidence for predictors of fluid responsiveness in children. A systematic search was performed using PubMed (1947–2013) and EMBASE (1974–2013). Search terms included fluid, volume, response, respond, challenge, bolus, load, predict, and guide. Results were limited to studies involving pediatric subjects (infant, child, and adolescent). Extraction of data was performed independently by 2 authors using predefined data fields, including study quality indicators. Any variable with an area under the receiver operating characteristic curve that was significantly above 0.5 was considered predictive. RESULTS: Twelve studies involving 501 fluid boluses in 438 pediatric patients (age range 1 day to 17.8 years) were included. Twenty-four variables were investigated. The only variable shown in multiple studies to be predictive was respiratory variation in aortic blood flow peak velocity (5 studies). Stroke volume index, stroke distance variation, and change in cardiac index (and stroke volume) induced by passive leg raising were found to be predictive in single studies only. Static variables based on heart rate, systolic arterial blood pressure, preload (central venous pressure, pulmonary artery occlusion pressure), thermodilution (global end diastolic volume index), ultrasound dilution (active circulation volume, central blood volume, total end diastolic volume, total ejection fraction), echocardiography (left ventricular end diastolic area), and Doppler (stroke volume index, corrected flow time) did not predict fluid responsiveness in children. Dynamic variables based on arterial blood pressure (systolic pressure variation, pulse pressure variation and stroke volume variation, difference between maximal or minimal systolic arterial blood pressure and systolic pressure at end-expiratory pause) and plethysmography (pulse oximeter plethysmograph amplitude variation) were also not predictive. There were contradicting results for plethymograph variation index and inferior vena cava diameter variation. CONCLUSIONS: Respiratory variation in aortic blood flow peak velocity was the only variable shown to predict fluid responsiveness in children. Static variables did not predict fluid responsiveness in children, which was consistent with evidence in adults. Dynamic variables based on arterial blood pressure did not predict fluid responsiveness in children, but the evidence for dynamic variables based on plethysmography was inconclusive.

Emergence delirium in children: a randomized trial to compare total intravenous anesthesia with propofol and remifentanil to inhalational sevoflurane anesthesia

Emergence delirium (ED) refers to a variety of behavioral disturbances commonly seen in children following emergence from anesthesia. Vapor‐based anesthesia with sevoflurane, the most common pediatric anesthetic technique, is associated with the highest incidence of ED. Propofol has been shown to reduce ED, but these studies have been methodologically limited.

An evaluation of a vibro-tactile display prototype for physiological monitoring.

Visual displays and auditory alarms are used to convey information on physiological variables in an operating room. However, the exponential growth in the number of physiological variables and the high probability of false alarms has amplified demands on the clinician’s attention. We have extended existing tactile technology to improve situational awareness and produce a practical clinical advisory device. A vibro-tactile display, using two vibrating motors applied to the volar surface of the forearm, was compared to an auditory alarm in a simulated clinical environment. Compared with auditory alarms, the vibro-tactile alarm was as easy to learn and had a better identification rate when used alone or combined with the auditory alarm. Most users preferred the vibro-tactile alarm although the prototype caused some discomfort. Furthermore, a combined vibro-tactile and auditory alarm had reduced accuracy when compared with the vibro-tactile alarm alone. The vibro-tactile modality shows considerable promise for clinical practice but will require further clinical testing and refinement, especially with regard to user comfort.

Robust closed-loop control of induction and maintenance of propofol anesthesia in children

During closed‐loop control, a drug infusion is continually adjusted according to a measure of clinical effect (e.g., an electroencephalographic depth of hypnosis (DoH) index). Inconsistency in population‐derived pediatric pharmacokinetic/pharmacodynamic models and the large interpatient variability observed in children suggest a role for closed‐loop control in optimizing the administration of intravenous anesthesia.

A framework for evaluating usability of clinical monitoring technology

Technology design is a complex task, and acceptability is enhanced when usability is central to its design. Evaluating usability is a challenge for purchasers and developers of technology. We have developed a framework for testing the usability of clinical monitoring technology through literature review and experience designing clinical monitors. The framework can help designers meet key international usability norms. The framework includes these direct testing methods: thinking aloud, question asking, co-discovery, performance and psychophysiological measurement. Indirect testing methods include: questionnaires and interviews, observation and ethnographic studies, and self-reporting logs. Inspection, a third usability testing method, is also included. The use of these methods is described and practical examples of how they would be used in the development of an innovative monitor are given throughout. This framework is built on a range of methods to ensure harmony between users and new clinical monitoring technology, and have been selected to be practical to use.

Design and Clinical Evaluation of Robust PID Control of Propofol Anesthesia in Children

This paper describes the design of a robust proportional-integral derivative (PID) controller for propofol infusion in children and presents the results of clinical evaluation of this closed-loop system during endoscopic investigations in children age 6-17. The controller design is based on a set of models that describes the interpatient variability in the response to propofol infusion in the study population. The PID controller is tuned to achieve sufficient robustness margins for the identified uncertainty. 108 children were enrolled in this study, and anesthesia was closed-loop controlled in 102 of these cases. Clinical evaluation of the system shows that closed-loop control of both induction and maintenance of anesthesia in children based on the WAVCNS index as a measure of clinical effect is feasible. A robustly tuned PID controller can accommodate the interpatient variability in children and spontaneous breathing can be maintained in most subjects.

Total intravenous anesthesia and spontaneous respiration for airway endoscopy in children – a prospective evaluation

Introduction:  Inhalational anesthesia with spontaneous respiration is traditionally used to facilitate airway endoscopy in children. The potential difficulties in maintaining adequate depth of anesthesia using inhalational anesthesia and the anesthetic pollution of the surgical environment are significant disadvantages of this technique. We report our institutional experience using total intravenous anesthesia (TIVA) and spontaneous respiration.

Relationship between age and spontaneous ventilation during intravenous anesthesia in children

Background:  Maintaining spontaneous ventilation in children, using total intravenous anesthesia (TIVA), is often desirable, particularly for airway endoscopy. The aim of this study was to evaluate the effect of age on the dose of remifentanil tolerated during spontaneous ventilation under anesthesia maintained with infusions of propofol and remifentanil and to provide guidelines for the administration of remifentanil and propofol to maintain spontaneous ventilation in children.