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.

Ketamine Prolonged Infusions in the Pediatric Intensive Care Unit: a Tertiary-Care Single-Center Analysis.

OBJECTIVE: Ketamine is commonly used as an anesthetic and analgesic agent for procedural sedation, but there is little evidence on its current use as a prolonged continuous infusion in the PICU. We sought to analyze the use of ketamine as a prolonged infusion in critically ill children, its indications, dosages, efficacy, and safety. METHODS: We retrospectively reviewed the clinical charts of patients receiving ketamine for ≥24 hours in the period 2017-2018 in our tertiary care center. Data on concomitant treatments pre and 24 hours post ketamine introduction and adverse events were also collected. RESULTS: Of the 60 patients included, 78% received ketamine as an adjuvant of analgosedation, 18% as an adjuvant of bronchospasm therapy, and 4% as an antiepileptic treatment. The median infusion duration was 103 hours (interquartile range [IQR], 58-159; range, 24-287), with median dosages between 15 (IQR, 10-20; range, 5-47) and 30 (IQR, 20-50; range, 10-100) mcg/kg/min. At 24 hours of ketamine infusion, dosages/kg/hr of opioids significantly decreased (p < 0.001), and 81% of patients had no increases in dosages of concomitant analgosedation. For 27% of patients with bronchospasm, the salbutamol infusions were lowered at 24 hours after ketamine introduction. Electroencephalograms of epileptic patients (n = 2) showed resolution of status epilepticus after ketamine administration. Adverse events most likely related to ketamine were hypertension (n = 1), hypersalivation (n = 1), and delirium (n = 1). CONCLUSIONS: Ketamine can be considered a worthy strategy for the analgosedation of difficult-to-sedate patients. Its use for prolonged sedation allows the sparing of opioids. Its efficacy in patients with bronchospasm or status epilepticus still needs to be investigated.

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.

Intranasal dexmedetomidine in pediatrics: update of current knowledge.

Intranasal dexmedetomidine, although still off-label, recently boasted an increasing consensus for different uses, namely, in diagnostic non-painful procedures, in painful procedures and in surgical premedication. However, at present, there is no consensus regarding indications, dosage and timing for administration. This article aims to provide a comprehensive literature analysis and summarize the more recent evidence of research on pediatric intranasal dexmedetomidine, in the effort to better delineate usefulness and limits for each specific indication. In summary, available pediatric evidence confirms efficacy and safety of dexmedetomidine for intranasal administration. Pharmacological profile for the various pediatric ages and procedures still needs quality studies and pharmacokinetic in-depth analysis.

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.

Light sedation with dexmedetomidine: a practical approach for the intensivist in different ICU patients.

Light sedation, corresponding to a Richmond Agitation-Sedation Scale between 0 and -1 is a priority of modern critical care practice. Dexmedetomidine, a highly selective, central, α2-adrenoceptor agonist, is increasingly administered in the intensive care units (ICUs) as an effective drug to induce light sedation, analgesia and a quasi-physiological sleep in critically ill patients. Although in general dexmedetomidine is well tolerated, side effects as bradycardia, hypertension, and hypotension may occur. Although a general dosing range is suggested, different ICU patients may require different and highly precise titration that may significantly vary due to neurological status, cardio-respiratory function, base-line blood pressure, heart rate, liver efficiency, age and co-administration of other sedatives. This review analyzes the use of dexmedetomidine in different settings including pediatric, adult, medical and surgical patients starting with some considerations on delirium prevention and sleep quality in critically ill patients and how dexmedetomidine may contribute to these crucial aspects. Dexmedetomidine use in specific sub-populations with unique characteristics will be detailed, with a special attention to a safe use.

A systematic review of methodology applied during preclinical anesthetic neurotoxicity studies: important issues and lessons relevant to the design of future clinical research.

UNLABELLED: Preclinical evidence suggests that anesthetic agents harm the developing brain thereby causing long-term neurocognitive impairments. It is not clear if these findings apply to humans, and retrospective epidemiological studies thus far have failed to show definitive evidence that anesthetic agents are harmful to the developing human brain. AIM: The aim of this systematic review was to summarize the preclinical studies published over the past decade, with a focus on methodological issues, to facilitate the comparison between different preclinical studies and inform better design of future trials. METHOD: The literature search identified 941 articles related to the topic of neurotoxicity. As the primary aim of this systematic review was to compare methodologies applied in animal studies to inform future trials, we excluded a priori all articles focused on putative mechanism of neurotoxicity and the neuroprotective agents. Forty-seven preclinical studies were finally included in this review. RESULTS: Methods used in these studies were highly heterogeneous-animals were exposed to anesthetic agents at different developmental stages, in various doses and in various combinations with other drugs, and overall showed diverse toxicity profiles. Physiological monitoring and maintenance of physiological homeostasis was variable and the use of cognitive tests was generally limited to assessment of specific brain areas, with restricted translational relevance to humans. CONCLUSION: Comparison between studies is thus complicated by this heterogeneous methodology and the relevance of the combined body of literature to humans remains uncertain. Future preclinical studies should use better standardized methodologies to facilitate transferability of findings from preclinical into clinical science.

Neurally adjusted ventilatory assist in weaning of neonates affected by congenital diaphragmatic hernia.

OBJECTIVE: The aim of the study is to evaluate the application of neurally adjusted ventilatory assist (NAVA) in the respiratory weaning of patients affected by congenital diaphragmatic hernia (CDH). METHODS: We analyzed the NAVA weaning in 12 neonates affected by CDH, relating the effectiveness of the electrical activation of the diaphragm (EAdi) signal to the type of CDH repair (with or without patch), the size of the patch, the stomach and His angle position, and the trend evaluation of some cardiorespiratory parameters with NAVA compared to pressure-support-ventilation (PSV). RESULTS: 5 neonates submitted to primary repair showed a regular EAdi signal and were successfully weaned with NAVA. Of the seven patients submitted to patch repair, five operated with patch limited to the diaphragmatic postero-lateral area had an active EAdi signal that permitted weaning with NAVA. Only in two neonates with hemidiaphragm agenesis was NAVA not feasible due to the impossibility to capture the EAdi signal. Compared to PSV, NAVA allows a significant improvement of oxygenation-linked indexes and paCO2, while PIP is reduced. CONCLUSION: Neonatal CDH with a postero-lateral diaphragmatic defect allows the NAVA catheter to obtain a correct EAdi signal and develop a viable NAVA ventilation. The lower risk of lung injury in NAVA appears compatible with current ventilatory strategies considered useful in CDH.