Efficacy and Safety of Dexmedetomidine for Prolonged Sedation in the PICU: A Prospective Multicenter Study (PROSDEX).

OBJECTIVES: We sought to evaluate dexmedetomidine efficacy in assuring comfort and sparing conventional drugs when used for prolonged sedation (≥24 hr) in critically ill patients, by using validated clinical scores while systematically collecting drug dosages. We also evaluated the safety profile of dexmedetomidine and the risk factors associated with adverse events. DESIGN: Observational prospective study. SETTING: Nine tertiary-care PICUs. PATIENTS: Patients less than 18 years who received dexmedetomidine for greater than or equal to 24 hours between January 2016 and December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-hundred sixty-three patients (median age, 13 mo; interquartile range, 4-71 mo) were enrolled. The main indication for dexmedetomidine use was as an adjuvant for drug-sparing (42%). Twenty-three patients (14%) received dexmedetomidine as monotherapy. Seven percent of patients received a loading dose. The median infusion duration was 108 hours (interquartile range, 60-168 hr), with dosages between 0.4 (interquartile range, 0.3-0.5) and 0.8 µg/kg/hr (interquartile range, 0.6-1.2 µg/kg/hr). At 24 hours of dexmedetomidine infusion, values of COMFORT-B Scale (n = 114), Withdrawal Assessment Tool-1 (n = 43) and Cornell Assessment of Pediatric Delirum (n = 6) were significantly decreased compared with values registered immediately pre dexmedetomidine (p < 0.001, p < 0.001, p = 0.027). Dosages/kg/hr of benzodiazepines, opioids, propofol, and ketamine were also significantly decreased (p < 0.001, p < 0.001, p = 0.001, p = 0.027). The infusion was weaned off in 85% of patients, over a median time of 36 hours (interquartile range, 12-48 hr), and abruptly discontinued in 15% of them. Thirty-seven percent of patients showed hemodynamic changes, and 9% displayed hemodynamic adverse events that required intervention (dose reduction in 79% of cases). A multivariate logistic regression model showed that a loading dose (odds ratio, 4.8; CI, 1.2-18.7) and dosages greater than 1.2 µg/kg/hr (odds ratio, 5.4; CI, 1.9-15.2) increased the odds of hemodynamic changes. CONCLUSIONS: Dexmedetomidine used for prolonged sedation assures comfort, spares use of other sedation drugs, and helps to attenuate withdrawal syndrome and delirium symptoms. Adverse events are mainly hemodynamic and are reversible following dose reduction. A loading dose and higher infusion dosages are independent risk factors for hemodynamic adverse events.

Withdrawal Assessment Tool-1 Monitoring in PICU: A Multicenter Study on Iatrogenic Withdrawal Syndrome.

OBJECTIVES: Withdrawal syndrome is an adverse reaction of analgesic and sedative therapy, with a reported occurrence rate between 17% and 57% in critically ill children. Although some factors related to the development of withdrawal syndrome have been identified, there is weak evidence for the effectiveness of preventive and therapeutic strategies. The main aim of this study was to evaluate the frequency of withdrawal syndrome in Italian PICUs, using a validated instrument. We also analyzed differences in patient characteristics, analgesic and sedative treatment, and patients' outcome between patients with and without withdrawal syndrome. DESIGN: Observational multicenter prospective study. SETTING: Eight Italian PICUs belonging to the national PICU network Italian PICU network. PATIENTS: One hundred thirteen patients, less than 18 years old, mechanically ventilated and treated with analgesic and sedative therapy for five or more days. They were admitted in PICU from November 2012 to May 2014. INTERVENTIONS: Symptoms of withdrawal syndrome were monitored with Withdrawal Assessment Tool-1 scale. MEASUREMENTS AND MAIN RESULTS: The occurrence rate of withdrawal syndrome was 64.6%. The following variables were significantly different between the patients who developed withdrawal syndrome and those who did not: type, duration, and cumulative dose of analgesic therapy; duration and cumulative dose of sedative therapy; clinical team judgment about analgesia and sedation's difficulty; and duration of analgesic weaning, mechanical ventilation, and PICU stay. Multivariate logistic regression analysis revealed that patients receiving morphine as their primary analgesic were 83% less likely to develop withdrawal syndrome than those receiving fentanyl or remifentanil. CONCLUSIONS: Withdrawal syndrome was frequent in PICU patients, and patients with withdrawal syndrome had prolonged hospital treatment. We suggest adopting the lowest effective dose of analgesic and sedative drugs and frequent reevaluation of the need for continued use. Further studies are necessary to define common preventive and therapeutic strategies.

Prognostic Value of the Area of Lung Involved in Severe and Non-Severe Bronchiolitis: An Observational, Ultrasound-Based Study.

BACKGROUND: Point of care lung ultrasound (LUS) has a definite role in viral bronchiolitis when combined with clinical data. Previous data showed a bigger involvement of the superior lung zones in more severe cases. The aim of the present study is to describe whether different lung areas are implicated to different degrees in patients admitted to a Pediatric Intensive Care Unit (PICU) and needing ventilation compared to those with less severe forms. METHODS: observational, prospective study. LUS scores of single lung areas and clinical data were collected for all children aged 0-12 months presenting with bronchiolitis to the participating centers and used as covariates for logistic regression having "PICU admission" as outcome. A subsequent analysis was carried out to investigate factors concurring with different lung zones' involvement. RESULTS: 173 patients were enrolled. Difficulty in feeding, presence of wheezing, SpO2 were all risk factors for PICU admission. Superior lung areas' LUS scores presented higher Odds Ratios for PICU admission and need for ventilation than inferior ones. Age and prematurity concurred in determining their higher LUS scores. CONCLUSIONS: Superior lobes' greater involvement could be favored by the geometrical distribution of relative bronchi, exiting with an acute angle from mainstem bronchi in small children where airway caliber is small and only small volumes of secretions can be occlusive.

Italian pediatric intensive care units admitting critically ill cancer children: results from a national survey.

BACKGROUND: Pediatric patients affected by oncologic disease have a significant risk of clinical deterioration that requires admission to the intensive care unit. This study reported the results of a national survey describing the characteristics of Italian onco-hematological units (OHUs) and pediatric intensive care units (PICUs) that admit pediatric patients, focusing on the high-complexity treatments available before PICU admission, and evaluating the approach to the end-of-life (EOL) when cared in a PICU setting. METHODS: A web-based electronic survey has been performed in April 2021, involving all Italian PICUs admitting pediatric patients with cancer participating in the study. RESULTS: Eighteen PICUs participated, with a median number of admissions per year of 350 (IQR 248-495). Availability of Extracorporeal Membrane Oxygenation therapy and the presence of intermediate care unit are the only statistically different characteristics between large or small PICUs. Different high-level treatments and protocols are performed in OHUs, non depending on the volume of PICU. Palliative sedation is mainly performed in the OHUs (78%), however, in 72% it is also performed in the PICU. In most centers protocols that address EOL comfort care and treatment algorithms are missing, non depending on PICU or OHU volume. CONCLUSIONS: A non-homogeneous availability of high-level treatments and in OHUs is described. Moreover, protocols addressing EOL comfort care and treatment algorithms in palliative care are lacking in many centers.

Connections Between Febrile Infection-Related Epilepsy Syndrome and Autoimmune Encephalitis. A Case Report of a Child With New Anti-neuronal Antibodies.

Acute encephalitis and febrile infection-related epilepsy syndrome (FIRES) are debilitating neurological disorders. It is increasingly accepted that FIRES should be considered an autoinflammation-mediated epileptic encephalopathy, but the debate about its etiopathogenesis is still very much open. Despite showing a considerable overlap with encephalitis, it continues to be regarded as a distinct entity. We describe the case of a previously healthy 5-year-old child who, following a fever, developed acute encephalopathy, status epilepticus, neurological, neuropsychological, and psychiatric manifestations, and claustrum involvement on MRI. At symptom onset, his clinical and instrumental data met the diagnostic criteria for both FIRES and acute encephalitis. He received benzodiazepines, levetiracetam, phenytoin, phenobarbital, thiopental, and first-line immunotherapy for acute inflammatory encephalopathy (intravenous methylprednisolone and immunoglobulins), without substantial improvement. Following the detection of anti-neuronal antibodies through immunohistochemistry performed on rat brain slices, he received therapeutic plasma exchange (TPE). His neurological and behavioral conditions improved drastically and his antibody titer fell sharply from the first to the last course of PE. Claustrum abnormalities on MRI disappeared. The patient's long-term outcome is favorable. At 13 months after discharge, he experienced a focal seizure and carbamazepine was started, achieving seizure control. At 10 years of age, he is still on carbamazepine, with well-controlled seizures, focal EEG abnormalities, and an otherwise normal neurological and cognitive profile and normal MRI. This case strengthens the view that FIRES might constitute the initial clinical presentation of a CNS inflammatory disease that could have, among multiple distinct etiologies, an autoimmune cause. Immunological and specific second- or third-level investigations including immunohistochemistry should be included in the diagnostic work up of patients with FIRES-like phenotypes. PE could be effective in this subset of patients, protecting them from long-term neurological sequelae.

The parental psychological distress caused by separation from their critically ill child during the COVID-19 pandemic: A tale of two cities.

Introduction: A child's critical illness is a stressful event for the entire family, causing significant emotional distress among parents and changes to family functioning. The Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) pandemic has abruptly caused modifications in visitation policies of Pediatric Intensive Care Units (PICUs) in many countries. We hypothesized that caregivers with no or severely restricted access to PICUs would demonstrate increased psychological distress as compared to those who had limitless access (LA) to PICUs. Methods: Sociodemographic variables, levels of psychological distress, ratings of family functioning, and ability to cope with stressful events were collected with an online survey in a group of caregivers after their child's hospitalization. Ratings of psychological distress were compared between caregivers with no/severely restricted (NA) and with LA to PICUs. Results: Measures of depression, anxiety, and global severity index (GSI) of psychological distress were significantly higher in NA caregivers as compared to LA. Among demographic characteristics of the sample, only gender influenced the severity of psychological symptoms: women showed an increased score on levels of somatization, depression, anxiety, and GSI. Avoidant coping style positively correlated with measures of depression. Univariate General Linear Model (GLM) analyses of the effects of sex, age, visitation policies of PICUs, and score of avoidant coping strategies on measures of psychological distress confirmed a significant univariate effect of no access to PICUs on parents' psychopathological scores. Conclusion: Restrictions imposed on visitation policies in PICU during the pandemic negatively impacted families' psychological wellbeing. A balance between the safety of patients, families, and health care professionals and meeting the needs of families is of utmost importance.

Very High Negative Concordance Rate of RT-PCR for SARS-CoV-2 in Nasopharyngeal Swab and Tracheo-Bronchial Aspirate in Children.

Reliable testing methods for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children are essential to allow normal activities. Diagnosis of SARS-CoV-2 infection is currently based on real-time reverse transcriptase-polymerase chain reaction (RT-PCR) performed on nasopharyngeal (NP) swabs; concerns have been raised regarding NP swab accuracy in children to detect the virus because of potential lack of cooperation of the patients or due to general uncertainties about concordance between high and low respiratory tract specimens in children. The aim of the study (IRB approval: ST/2020/405) is to prospectively compare RT-PCR results on NP and tracheo-bronchial aspirate (TA) in children admitted to the hospital for surgery or admitted to the Pediatric Intensive Care Unit (PICU) of a tertiary children hospital in Milano, Italy, during a peak of COVID-19 infections in the city. A total of 385 patients were enrolled in the study: 364 from surgical theater and 21 from PICU. Two patients (0.5%) tested positive on TA and were negative on NP; both cases occurred in November 2020, during a peak of infection in the city. Specificity of NP swab was.995 (95% CI: 0.980-0.999). Two patients with positive NP swabs tested negative on TA. Conclusion: Our study shows that the specificity of SARS-CoV-2 RT-PCR on TA swab, compared to results of SARS-CoV-2 RT-PCR on NP, was very high for negative cases in our pediatric cohort during a period of high epidemiological pressure.

Lung Ultrasound Patterns in Multisystem Inflammatory Syndrome in Children (MIS-C)-Characteristics and Prognostic Value.

Objective and design: Following COVID-19 infection, children can develop an hyperinflammatory state termed Multisystem Inflammatory Syndrome in Children (MIS-C). Lung Ultrasound (LUS) features of COVID-19 in children have been described, but data describing the LUS findings of MIS-C are limited. The aim of this retrospective observational study conducted between 1 March and 31 December 2020, at a tertiary pediatric hospital in Milano, is to describe LUS patterns in patients with MIS-C and to verify correlation with illness severity. The secondary objective is to evaluate concordance of LUS with Chest X-ray (CXR). Methodology: Clinical and laboratory data were collected for all patients (age 0−18 years) admitted with MIS-C, as well as LUS and CXR patterns at admission. PICU admission, needed for respiratory support and inotrope administration, hospital, and PICU length of stay, were considered as outcomes and evaluated in the different LUS patterns. An agreement between LUS and CXR evaluation was assessed with Cohen' k. Results: 24 children, who had a LUS examination upon admission, were enrolled. LUS pattern of subpleural consolidations < or > 1 cm with or without pleural effusion were associated with worse Left Ventricular Ejection Fraction at admission and need for inotropes. Subpleural consolidations < 1 cm were also associated with PICU length of stay. Agreement of CXR with LUS for consolidations and effusion was slight. Conclusion: LUS pattern of subpleural consolidations and consolidations with or without pleural effusion are predictors of disease severity; under this aspect, LUS can be used at admission to stratify risk of severe disease.

Prolonged sedation in critically ill children: is dexmedetomidine a safe option for younger age? An off-label experience.

BACKGROUND: Dexmedetomidine (DEX) is an alpha-2-adrenergic agonist, recently approved by Italian-Medicines-Agency for difficult sedation in pediatrics, but few data exist regarding prolonged infusions in critically-ill children, especially in younger ages. Aim of our study was to evaluate DEX use and safety for prolonged sedation in Pediatric Intensive Care Units (PICUs). METHODS: Patients receiving DEX for ≥24 hours were retrospectively evaluated to analyze DEX indications, dosages, use of analgesics or sedatives, adverse events (AEs), withdrawal syndrome or delirium. RESULTS: Forty-seven patients (median 0.7years) from nine PICUs were enrolled. Main indications were adjuvant for drugs sparing (59.6%) and for analgosedation weaning (36.2%). Median infusion duration was 82.0 hours (IQR 62.2-126.0), with dosages between 0.4 (IQR 0.2-0.5) and 0.8 mcg/kg/h (IQR 0.6-1.2). Fifty-nine-percent of patients received other sedatives, 83% other analgesics. Twenty-one-percent presented withdrawal syndrome, 4.2% delirium, none of them DEX-related. Forty-six-percent experienced a potentially-DEX-related AE. AEs were all hemodynamic, 14.9% requiring intervention but none DEX interruption. The median minimum and maximum dosages were significantly higher in patients with AEs (0.5 vs. 0.3,P=0.001; 1.0 vs. 0.7,P<0.001), without correlations with the infusion duration. AEs rate was higher in patients receiving benzodiazepines (P=0.020) or more than one analgesic (P=0.003) and in those presenting withdrawal syndrome (P<0.001). CONCLUSIONS: DEX was confirmed as useful and relatively safe drug for prolonged sedation in critically-ill children, particularly in younger ages. Main AEs were cardiovascular, reversible, related with higher doses, with the concomitant use of benzodiazepines or multiple sedation drugs and with the presence of withdrawal syndrome.