The newborn infant parasympathetic evaluation in pediatric and neonatology: a literature review.

PURPOSE: The Newborn Infant Parasympathetic Evaluation (NIPE) is a heart rate variability-based technology for assessing pain and comfort in neonates and infants under 2-years-old. This review aims to investigate the clinical utility of the NIPE. METHODS: Two investigators screened Pubmed/Medline and Google Scholar for relevant studies, independently. One investigator extracted data, which were reviewed by a second investigator. RESULTS: The NIPE was used during/after painful stimuli (6 studies), in the context of general anaesthesia (2 studies), and for comfort assessment (6 studies). A) Evaluation of procedural pain/distress: 2 studies reported that the mean-NIPE could be used for reliable monitoring of prolonged pain, and one study reported the association between instant-NIPE and pain after a stimulus but the instant-NIPE represents the NIPE average over 3 min. Two studies found no correlation between the NIPE and comfort behavior/pain scales, but they mainly differed in patients' gestational age and evaluation methodology. B) There are only 2 studies for the evaluation of nociception during surgery under general anaesthesia with contradictory results. C) Studies assessing neonates' comfort reported increased NIPE scores during skin-to-skin contact and during facilitated tucking associated with a human voice. No effect on NIPE scores of facilitated tucking during echocardiography was reported in preterm infants. One study reported significantly different NIPE scores with 2 surfactant therapy protocols. Overall, study populations were small and heterogeneous. CONCLUSION: The results regarding NIPE's performances differ between studies. Given the limited number of studies and the heterogeneous outcomes, more studies are required to confirm the NIPE usefulness in the different clinical settings.

Outcome and characteristics of invasive fungal infections in critically ill burn patients: A multicenter retrospective study.

BACKGROUND: Characteristics and outcome of invasive fungal infection (IFI) in critically ill burn patients have been poorly explored. OBJECTIVES: We report the factors associated with 90-day mortality in a multicentre retrospective European study. PATIENTS/METHODS: All burn patients with confirmed IFI admitted between 1 January 2010 to 31 December 2015 in 10 centres in France and Belgium were included. RESULTS: Ninety-four patients were enrolled with 110 cases of IFIs: 79 (71.8%) were yeasts IFI and 31 (28.2%) filamentous IFI. Incidence was 1% among admitted patients. The 90-day mortality was 37.2% for all IFIs combined, 52% for filamentous infection and 31.9% for yeast infection. Patients with more than one IFI had a higher 90-day mortality than patients with only one episode (61.5% vs 33.5% (P = .006)). In multivariate analysis, higher Simplified Acute Physiology Score II (OR = 1.05 (95% CI: 1.02-1.09) P = .003), bacterial co-infection (OR = 3.85 (95% CI: 1.23-12.01), P = .014) and use of skin allografts at the time of IFI diagnosis (OR = 3.87 (95% CI: 1.31-11.42), P = .021) were associated with 90-day mortality. CONCLUSIONS: Although rare, invasive fungal infections remain associated with poor outcome in burn patients. Bacterial co-infection and presence of allograft were potentially modifiable factors independently associated with outcome.

[Management of severe burn pain]. / Prise en charge de la douleur du brûlé grave.

The experience of pain during a severe burn is multifactorial, both in the typology of the burn and in the circumstances of its occurrence. Third-degree burns are painless as the dermis and its nociception sensors are damaged. After a severe burn, from initial management, to home care, to a long hospital stay, pain evolves with its etiology and requires specific management.

Detection of Circulating Mucorales DNA in Critically Ill Burn Patients: Preliminary Report of a Screening Strategy for Early Diagnosis and Treatment.

BACKGROUND: Invasive wound mucormycosis (IWM) is associated with an extremely poor outcome among critically ill burn patients. We describe the detection of circulating Mucorales DNA (cmDNA) for the early diagnosis of IWM in those patients and report the potential value of detecting cmDNA for treatment guidance. METHODS: Severely ill burn patients admitted to our tertiary referral center between October 2013 and February 2016 were included. Retrospective plasma samples were tested for the presence of cmDNA by quantitative real-time polymerase chain reaction (qPCR). Patients were then prospectively screened twice a week, and liposomal amphotericin-B therapy initiated based on a positive qPCR. The primary endpoint was the time between cmDNA detection and standard diagnosis. Secondary endpoints were the time from cmDNA detection and treatment initiation and mortality. RESULTS: Seventy-seven patients (418 samples) were included. The average age was 46 (28-60) years, abbreviated burn severity index was 8 (7-10), and simplified acute physiology score was 33 (23-46). The total body surface area was 33% (22%-52%). cmDNA was detected 11 (4.5-15) days before standard diagnosis. The in-hospital mortality was 62% for patients with IWM and 24% for those without (P = .03). The mortality due to IWM was 80% during period A and 33% during period B (P = .46). CONCLUSIONS: This study suggests that the detection of cmDNA allows earlier diagnosis of IWM in severely ill burn patients and earlier initiation of treatment. Further studies are needed to confirm the impact of earlier treatment initiation on patient outcome.

[Analysing heart rate variability to improve the monitoring of pain]. / Analyser la variabilité de la fréquence cardiaque pour mieux monitorer la douleur.

An innovative technique based on the analysis of instantaneous heart rate variability helps to improve the prevention and management of pain and discomfort. Simple to implement, this non-invasive technique is based on the continuous recording of the electrocardiograph signal.

A substitution method to improve completeness of events documentation in anesthesia records.

AIMS are optimized to find and display data and curves about one specific intervention but is not retrospective analysis on a huge volume of interventions. Such a system present two main limitation; (1) the transactional database architecture, (2) the completeness of documentation. In order to solve the architectural problem, data warehouses were developed to propose architecture suitable for analysis. However, completeness of documentation stays unsolved. In this paper, we describe a method which allows determining of substitution rules in order to detect missing anesthesia events in an anesthesia record. Our method is based on the principle that missing event could be detected using a substitution one defined as the nearest documented event. As an example, we focused on the automatic detection of the start and the end of anesthesia procedure when these events were not documented by the clinicians. We applied our method on a set of records in order to evaluate; (1) the event detection accuracy, (2) the improvement of valid records. For the year 2010-2012, we obtained event detection with a precision of 0.00 (-2.22; 2.00) min for the start of anesthesia and 0.10 (0.00; 0.35) min for the end of anesthesia. On the other hand, we increased by 21.1% the data completeness (from 80.3 to 97.2% of the total database) for the start and the end of anesthesia events. This method seems to be efficient to replace missing "start and end of anesthesia" events. This method could also be used to replace other missing time events in this particular data warehouse as well as in other kind of data warehouses.

Ventilation practices in burn patients-an international prospective observational cohort study.

BACKGROUND: It is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from it. This study aimed to determine ventilation practices in burn intensive care units (ICUs) and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28 (VFD-28). METHODS: This is an international prospective observational cohort study including adult burn patients requiring mechanical ventilation. Low tidal volume (V T) was defined as V T ≤ 8 mL/kg predicted body weight (PBW). Levels of positive end-expiratory pressure (PEEP) and maximum airway pressures were collected. The association between V T and VFD-28 was analyzed using a competing risk model. Ventilation settings were presented for all patients, focusing on the first day of ventilation. We also compared ventilation settings between patients with and without inhalation trauma. RESULTS: A total of 160 patients from 28 ICUs in 16 countries were included. Low V T was used in 74% of patients, median V T size was 7.3 [interquartile range (IQR) 6.2-8.3] mL/kg PBW and did not differ between patients with and without inhalation trauma (p = 0.58). Median VFD-28 was 17 (IQR 0-26), without a difference between ventilation with low or high V T (p = 0.98). All patients were ventilated with PEEP levels ≥5 cmH2O; 80% of patients had maximum airway pressures <30 cmH2O. CONCLUSION: In this international cohort study we found that lung-protective ventilation is used in the majority of burn patients, irrespective of the presence of inhalation trauma. Use of low V T was not associated with a reduction in VFD-28. TRIAL REGISTRATION: Clinicaltrials.gov NCT02312869. Date of registration: 9 December 2014.

The A2B trial, antibiotic prophylaxis for excision-graft surgery in burn patients: a multicenter randomized double-blind study.

BACKGROUND: The indication for antibiotic prophylaxis in burn patients remains highly controversial, with no consensus having been reached. The objective of antibiotic prophylaxis is to reduce the risk of postoperative local and systemic infections. Burn surgery is associated with a high incidence of bacteremia, postoperative infections, and sepsis. However, antibiotic prophylaxis exposes patients to the risk of selecting drug-resistant pathogens as well as to the adverse effects of antibiotics (i.e., Clostridium difficile colitis). The lack of data precludes any strong international recommendations regarding perioperative prophylaxis using systemic antibiotics in this setting. The goal of this project is therefore to determine whether perioperative systemic antibiotic prophylaxis can reduce the incidence of postoperative infections in burn patients. METHODS: The A2B trial is a multicenter (10 centers), prospective, randomized, double-blinded, placebo-controlled study. The trial will involve the recruitment of 506 adult burn patients with a total body surface area (TBSA) burn of between 5 and 40% and requiring at least one excision-graft surgery for deep burn injury. Participants will be randomized to receive antibiotic prophylaxis (antibiotic prophylaxis group) or a placebo (control group) 30 min before the incision of the first two surgeries. The primary outcome will be the occurrence of postoperative infections defined as postoperative sepsis and/or surgical site infection and/or graft lysis requiring a new graft within 7 days after surgery. Secondary outcomes will include mortality at day 90 postrandomization, skin graft lysis requiring a new graft procedure, postoperative bacteremia (within 48 h of surgery), postoperative sepsis, postoperative surgical site infection, number of hospitalizations until complete healing (> 95% TBSA), number of hospitalization days living without antibiotic therapy at day 28 and day 90, and multiresistant bacterial colonization or infection at day 28 and day 90. DISCUSSION: The trial aims to provide evidence on the efficacy and safety of antibiotic prophylaxis for excision-graft surgery in burn patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04292054 . Registered on 2 March 2020.

Management of severe thermal burns in the acute phase in adults and children.

OBJECTIVES: To provide recommendations to facilitate the management of severe thermal burns during the acute phase in adults and children. DESIGN: A committee of 20 experts was asked to produce recommendations in six fields of burn management, namely, (1) assessment, admission to specialised burns centres, and telemedicine; (2) haemodynamic management; (3) airway management and smoke inhalation; (4) anaesthesia and analgesia; (5) burn wound treatments; and (6) other treatments. At the start of the recommendation-formulation process, a formal conflict-of-interest policy was developed and enforced throughout the process. The entire process was conducted independently of any industry funding. The experts drew up a list of questions that were formulated according to the PICO model (Population, Intervention, Comparison, and Outcomes). Two bibliography experts per field analysed the literature published from January 2000 onwards using predefined keywords according to PRISMA recommendations. The quality of data from the selected literature was assessed using GRADE® methodology. Due to the current paucity of sufficiently powered studies regarding hard outcomes (i.e. mortality), the recommendations are based on expert opinion. RESULTS: The SFAR guidelines panel generated 24 statements regarding the management of acute burn injuries in adults and children. After two scoring rounds and one amendment, strong agreement was reached for all recommendations. CONCLUSION: Substantial agreement was reached among a large cohort of experts regarding numerous strong recommendations to optimise the management of acute burn injuries in adults and children.

Mucormycosis in Burn Patients.

Patients with extensive burns are an important group at risk for cutaneous mucormycosis. This study aimed to perform a systematic review of all reported mucormycosis cases in burn patients from 1990 onward. A Medline search yielded identification of 7 case series, 3 outbreaks, and 25 individual cases reports. The prevalence reached 0.04%⁻0.6%. The median age was 42⁻48 in the case series and outbreaks, except for the studies from military centers (23.5⁻32.5) and in individual reports (29.5). The median total body surface area reached 42.5%⁻65%. Various skin lesions were described, none being pathognomonic: the diagnosis was mainly reached because of extensive necrotic lesions sometimes associated with sepsis. Most patients were treated with systemic amphotericin B or liposomal amphotericin B, and all underwent debridement and/or amputation. Mortality reached 33%⁻100% in the case series, 29%⁻62% during outbreaks, and 40% in individual cases. Most patients were diagnosed using histopathology and/or culture. Mucorales qPCR showed detection of circulating DNA 2⁻24 days before the standard diagnosis. Species included the main clinically relevant mucorales (i.e., Mucor, Rhizopus, Absidia/Lichtheimia, Rhizomucor) but also more uncommon mucorales such as Saksenaea or Apophysomyces. Contact with soil was reported in most individual cases. Bandages were identified as the source of contamination in two nosocomial outbreaks.

Automated Data Aggregation for Time-Series Analysis: Study Case on Anaesthesia Data Warehouse.

Data stored in operational databases are not reusable directly. Aggregation modules are necessary to facilitate secondary use. They decrease volume of data while increasing the number of available information. In this paper, we present four automated engines of aggregation, integrated into an anaesthesia data warehouse. Four instances of clinical questions illustrate the use of those engines for various improvements of quality of care: duration of procedure, drug administration, assessment of hypotension and its related treatment.

Measurement of Heart Rate Variability to Assess Pain in Sedated Critically Ill Patients: A Prospective Observational Study.

INTRODUCTION: The analgesia nociception index (ANI) assesses the relative parasympathetic tone as a surrogate for antinociception/nociception balance in sedated patients. The aim of this study is to determine the effectiveness of ANI in detecting pain in deeply sedated critically ill patients. METHODS: This prospective observational study was performed in two medical ICUs. All patients receiving invasive mechanical ventilation and deep sedation were eligible. In all patients, heart rate and ANI were continuously recorded using the Physiodoloris® device during 5 minutes at rest (T1), during a painful stimulus (T2), and during 5 minutes after the end of the painful stimulus (T3). The chosen painful stimulus was patient turning for washstand. Pain was evaluated at T2, using the behavioral pain scale (BPS). The primary objective was to determine the effectiveness of ANI in detecting pain. Secondary objectives included the impact of norepinephrine on the effectiveness of ANI in detecting pain, and the correlation between ANI and BPS. RESULTS: Forty-one patients were included. ANI was significantly lower at T2 (Med (IQR) 69(55-78)) compared with T1 (85(67-96), p<0.0001), or T3 (81(63-89), p<0.0001). Similar results were found in the subgroups of patients with (n = 21) or without (n = 20) norepinephrine. ANI values were significantly higher in patients with norepinephrine compared with those without norepinephrine at T1, and T2. No significant correlation was found between ANI and BPS at T2. CONCLUSIONS: ANI is effective in detecting pain in deeply sedated critically ill patients, including those patients treated with norepinephrine. No significant correlation was found between ANI and BPS.

Assessment of Procedural Pain in Children Using Analgesia Nociception Index: A Pilot Study.

OBJECTIVES: The Analgesia Nociception Index (ANI), based on heart rate (HR) variability analysis, is known to decrease after a painful stimulus during surgery under general anesthesia in adults. It is measured continuously and noninvasively. We studied ANI response to procedural pain in a pediatric population and ANI measurement's feasibility in this context, across age. METHODS: A prospective, noninterventional pilot study was performed. All children (between 6 mo and under 18 y) undergoing muscle biopsy conducted under analgesia and light sedation were included. Medical staff was blind to the ANI monitor. HR and ANI were recorded and analyzed during 2 periods: T1 before incision and T2 after incision. Pain was assessed by the FLACC scale at T2. We observed ANI and HR variations after incision. ANI, HR, and FLACC were compared between children younger or older than 6 years. Enrollment or technical issues were reported. RESULTS: A total of 26 children were included (median age, 6 y; ranging from 6 mo to 16 y; 16 male). ANI decreased from T1 to T2. HR, ANI, or FLACC values were not different in children younger or older than 6 years. No parents or children refused to take part in the study. No technical issues was reported. DISCUSSION: In this pilot study, ANI measurement seems relevant in pediatric procedural pain, across age. Further studies are needed to confirm these results.

Methodology to automatically detect abnormal values of vital parameters in anesthesia time-series: Proposal for an adaptable algorithm.

Abnormal values of vital parameters such as hypotension or tachycardia may occur during anesthesia and may be detected by analyzing time-series data collected during the procedure by the Anesthesia Information Management System. When crossed with other data from the Hospital Information System, abnormal values of vital parameters have been linked with postoperative morbidity and mortality. However, methods for the automatic detection of these events are poorly documented in the literature and differ between studies, making it difficult to reproduce results. In this paper, we propose a methodology for the automatic detection of abnormal values of vital parameters. This methodology uses an algorithm allowing the configuration of threshold values for any vital parameters as well as the management of missing data. Four examples illustrate the application of the algorithm, after which it is applied to three vital signs (heart rate, SpO2, and mean arterial pressure) to all 2014 anesthetic records at our institution.

Variations of the analgesia nociception index during propofol anesthesia for total knee replacement.

OBJECTIVE: The Analgesia Nociception Index (ANI) monitor measures the relative parasympathetic tone as a surrogate for the antinociception/nociception balance during general anesthesia. The aims of this observational study were to test whether ANI could early detect hemodynamic reactivity (HemodR) during propofol anesthesia, measure pain in conscious patients after surgery, and determine ANI predictive thresholds. MATERIALS AND METHODS: After institutional approval and informed consent, adult patients scheduled for total knee replacement were included. Propofol was administered using a target-controlled infusion device, and sufentanil was administered at induction and in case of "HemodR," defined as a 20% increase in heart rate or systolic blood pressure. Data were collected before the start of surgery (NoStim), in case of "HemodR," and after awakening before and after the pain had been treated by truncular analgesia. Nonparametric tests were conducted. Thresholds were determined using an receiver operating characteristic analysis. Results are presented as median (interquartile range). RESULTS: A total of 27 patients have been analysed. ANI decreased from 82 (30) at "NoStim" to 47 (22) at "HemodR," whereas heart rate increased moderately from 61 (14) to 65 (18) and systolic blood pressure increased significantly from 91 mm Hg (16 mm Hg) to 151 mm Hg (25 mm Hg). Receiver operating characteristic analysis led to a threshold of 63 for "HemodR" detection (sensitivity=80%, specificity=88%, area under the curve=0.92), whereas ANI performance in awake patients was lower. DISCUSSION: ANI measures during propofol anesthesia are coherent with the evolution of the analgesia/nociception balance, although its performance decreases in awake patients. Further clinical validation should focus on demonstrating the benefit of maintaining ANI over 63 during surgery.

Newborn infant pain assessment using heart rate variability analysis.

OBJECTIVES: Systems controlling cardiovascular function are closely coupled with the perception of pain. Heart rate variability (HRV) is a well-established noninvasive measure of cardiac autonomic control. We hypothesized that pain may alter HRV in the newborn infant and that HRV analysis could be used as an indicator of prolonged pain in the newborn infant. METHODS: To test the hypothesis, we measured the magnitude of the heart rate high-frequency variations using an innovative High Frequency Variability Index (HFVI) in newborn infants at risk of postoperative pain. We investigated newborn infants with a gestational age (GA) more than 34 weeks, and who were admitted after a major surgical procedure. Inclusions ranged from 2 to 72 hours after the surgery. The postoperative pain was scored using EDIN scale (neonatal pain and discomfort scale) at the end of the 2 hours recording period. The infants were separated in: (1) Group "Low EDIN," when EDIN<5; and (2) Group "High EDIN," when EDIN >=5. Predictive positive and negative values of a threshold value of HFVI in assessing pain have been studied. RESULTS: Twenty-eight newborn infants were enrolled in the study (mean GA=37.8+/-1.5 wk) at a median delay between the surgery and the recording of 5 hours. Mean EDIN were 2+/-1 and 7+/-2 in respectively the groups "Low EDIN" and "High EDIN." The 2 groups were similar for GA, basal heart and respiratory rates, SpO2, mean arterial blood pressure, and morphine infusion rate. HFVI was significantly lower in the group "High EDIN" than in the group "Low EDIN" (0.7+/-0.2 vs. 1.2+/-0.3, respectively; P<0.01). An HFVI <0.9 was able to predict an EDIN score >=5, with a sensitivity of 90%, and a specificity of 75%. DISCUSSION: The results of this study indicate that postoperative pain is associated with a decreased high-frequency HRV in full-term newborn infants. Our findings suggest that HRV could be used as an indicator to assess prolonged pain in the newborn infants.