K-Means Clustering for Shock Classification in Pediatric Intensive Care Units.

Shock is described as an inadequate oxygen supply to the tissues and can be classified in multiple ways. In clinical practice still, old methods are used to discriminate these shock types. This article proposes the application of unsupervised classification methods for the stratification of these patients in order to treat them more appropriately. With a cohort of 90 patients admitted in pediatric intensive care units (PICU), the k-means algorithm was applied in the first 24 h data since admission (physiological and analytical variables and the need for devices), obtaining three main groups. Significant differences were found in variables used (e.g., mean diastolic arterial pressure p < 0.001, age p < 0.001) and not used for training (e.g., EtCO2 min p < 0.001, Troponin max p < 0.01), discharge diagnosis (p < 0.001) and outcomes (p < 0.05). Clustering classification equaled classical classification in its association with LOS (p = 0.01) and surpassed it in its association with mortality (p < 0.04 vs. p = 0.16). We have been able to classify shocked pediatric patients with higher outcome correlation than the clinical traditional method. These results support the utility of unsupervised learning algorithms for patient classification in PICU.

Multicenter randomized clinical trial comparing dexamethasone versus placebo in preventing upper airway obstruction after extubation in critically ill children.

To analyze the effectiveness of dexamethasone in preventing upper airway obstruction (UAO) symptoms after extubation and the need of reintubation in critically ill children. Multicenter, prospective, double-blind, randomized, phase IV clinical trial involving five pediatric intensive care units. Children between 1 month and 16 years-of-age intubated for more than 48 h were included. Patients were randomized to receive placebo or dexamethasone 0.25 mg/kg every 6 h, 6-to-12 h prior to extubation (four doses). 48 h follow-up was carried out after extubation. Severity of UAO symptoms (Taussig score, stridor) and reintubation requirement were compared. 147 patients were randomized (10 were excluded), 70 patients received dexamethasone and 67 placebo. No global differences were found in the presence of stridor or moderate-to-severe UAO symptoms (Taussig ≥ 5), but Taussig ≥ 5 was less frequent in patients less than 2 years-of-age treated with steroids (p = 0.014). Median Taussig score was lower in the dexamethasone group 1 h after extubation, p < 0.001. 27 patients required reintubation, 9 due to UAO: 3 (4.3%) in the dexamethasone group and 6 (8.9%) in the placebo group, p = 0.319. In those intubated > 5 days, reintubation due to UAO was higher in the placebo group (2.4% vs. 14.3, p = 0.052). Nebulized epinephrine and budesonide were required more frequently in the placebo group in the first 2 h (p = 0.041) and 1 h (p = 0.02) after extubation, respectively. No relevant side effects were observed. Dexamethasone prior to extubation did not significantly reduce moderate-severe UAO symptoms, except for patients under 2-years of age. Dexamethasone could decrease Taussig score and the need of rescue therapies, as well as reintubation rates in those intubated for more than 5 days.

Severe manifestations of SARS-CoV-2 in children and adolescents: from COVID-19 pneumonia to multisystem inflammatory syndrome: a multicentre study in pediatric intensive care units in Spain.

BACKGROUND: Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection in children. We aimed to describe the characteristics of children admitted to Pediatric Intensive Care Units (PICUs) presenting with MIS-C in comparison with those admitted with SARS-CoV-2 infection with other features such as COVID-19 pneumonia. METHODS: A multicentric prospective national registry including 47 PICUs was carried out. Data from children admitted with confirmed SARS-CoV-2 infection or fulfilling MIS-C criteria (with or without SARS-CoV-2 PCR confirmation) were collected. Clinical, laboratory and therapeutic features between MIS-C and non-MIS-C patients were compared. RESULTS: Seventy-four children were recruited. Sixty-one percent met MIS-C definition. MIS-C patients were older than non-MIS-C patients (p = 0.002): 9.4 years (IQR 5.5-11.8) vs 3.4 years (IQR 0.4-9.4). A higher proportion of them had no previous medical history of interest (88.2% vs 51.7%, p = 0.005). Non-MIS-C patients presented more frequently with respiratory distress (60.7% vs 13.3%, p < 0.001). MIS-C patients showed higher prevalence of fever (95.6% vs 64.3%, p < 0.001), diarrhea (66.7% vs 11.5%, p < 0.001), vomits (71.1% vs 23.1%, p = 0.001), fatigue (65.9% vs 36%, p = 0.016), shock (84.4% vs 13.8%, p < 0.001) and cardiac dysfunction (53.3% vs 10.3%, p = 0.001). MIS-C group had a lower lymphocyte count (p < 0.001) and LDH (p = 0.001) but higher neutrophil count (p = 0.045), neutrophil/lymphocyte ratio (p < 0.001), C-reactive protein (p < 0.001) and procalcitonin (p < 0.001). Patients in the MIS-C group were less likely to receive invasive ventilation (13.3% vs 41.4%, p = 0.005) but were more often treated with vasoactive drugs (66.7% vs 24.1%, p < 0.001), corticosteroids (80% vs 44.8%, p = 0.003) and immunoglobulins (51.1% vs 6.9%, p < 0.001). Most patients were discharged from PICU by the end of data collection with a median length of stay of 5 days (IQR 2.5-8 days) in the MIS-C group. Three patients died, none of them belonged to the MIS-C group. CONCLUSIONS: MIS-C seems to be the most frequent presentation among critically ill children with SARS-CoV-2 infection. MIS-C patients are older and usually healthy. They show a higher prevalence of gastrointestinal symptoms and shock and are more likely to receive vasoactive drugs and immunomodulators and less likely to need mechanical ventilation than non-MIS-C patients.

Addition of terlipressin to initial volume resuscitation in a pediatric model of hemorrhagic shock improves hemodynamics and cerebral perfusion.

Hemorrhagic shock is one of the leading causes of mortality and morbidity in pediatric trauma. Current treatment based on volume resuscitation is associated to adverse effects, and it has been proposed that vasopressors may be used in the pharmacological management of trauma. Terlipressin has demonstrated its usefulness in other pediatric critical care scenarios and its long half-life allows its use as a bolus in an outpatient critical settings. The aim of this study was to analyze whether the addition of a dose of terlipressin to the initial volume expansion produces an improvement in hemodynamic and cerebral perfusion at early stages of hemorrhagic shock in an infant animal model. We conducted an experimental randomized animal study with 1-month old pigs. After 30 minutes of hypotension (mean arterial blood pressure [MAP]<45 mmHg) induced by the withdrawal of blood over 30 min, animals were randomized to receive either normal saline (NS) 30 mL/kg (n = 8) or a bolus of 20 mcg/kg of terlipressin plus 30 mL/kg of normal saline (TP) (n = 8). Global hemodynamic and cerebral monitoring parameters, brain damage markers and histology samples were compared. After controlled bleeding, significant decreases were observed in MAP, cardiac index (CI), central venous pressure, global end-diastolic volume index (GEDI), left cardiac output index, SvO2, intracranial pressure, carotid blood flow, bispectral index (BIS), cerebral perfusion pressure (CPP) and increases in systemic vascular resistance index, heart rate and lactate. After treatment, MAP, GEDI, CI, CPP and BIS remained significantly higher in the TP group. The addition of a dose of terlipressin to initial fluid resuscitation was associated with hemodynamic improvement, intracranial pressure maintenance and better cerebral perfusion, which would mean protection from ischemic injury. Brain monitoring through BIS was able to detect changes caused by hemorrhagic shock and treatment.

Combined Cerebral and Renal Near-Infrared Spectroscopy After Congenital Heart Surgery.

The maintenance of an adequate oxygen supply to tissues after congenital heart surgery is essential for good outcomes. The objective of this study was to assess the usefulness of near-infrared spectroscopy (NIRS) for estimating central venous oxygen saturation (ScvO2) using both cerebral and renal measurements, explore its relation with cardiac output measurements and check its ability to detect low cardiac output. A prospective observational pilot study was conducted in patients weighing <10 kg undergoing cardiopulmonary bypass surgery. Spectroscopy probes were placed on the forehead and renal area, and serial cardiac output measurements were obtained by femoral transpulmonary thermodilution over the first 24 h after surgery. In the 15 patients studied, ScvO2 was correlated with cerebral (r = 0.58), renal (r = 0.60) and combined (r = 0.71) measurements. Likewise, the systolic index was correlated with the NIRS signals: cerebral (r = 0.60), renal (r = 0.50) and combined (r = 0.66). Statistically significant differences were found in the NIRS measures registered in the 29 low cardiac output events detected by thermodilution: cerebral: 62 % (59-65) versus 69 % (63-76); renal: 83 % (70-89) versus 89 % (83-95); and combined 64 % (60-69) versus 72 % (67-76). In our series, combined cerebral and renal monitoring was correlated with central venous oxygen saturation and cardiac output; low cardiac output detection associated a different spectroscopy pattern.

Cardiac index monitoring by femoral arterial thermodilution after cardiac surgery in children.

PURPOSE: The aim of this study is to determine whether the maintenance of cardiac index (CI) measured by femoral arterial thermodilution during the postoperative period after heart surgery in children is related to short-term outcome. MATERIALS AND METHODS: A prospective observational study in a pediatric intensive care unit at a referral hospital for congenital heart disease was conducted. Thirty-five children after open heart surgery were monitored in 5 planned times with PiCCO (Pulsion Medical System AG, Munich, Germany) during the first 24 hours after admission. Normal CI was defined as 3 L min(-1) m(-2) or greater. RESULTS: Eighteen patients hold CI at every measurement point. In this group, the median stay in the pediatric intensive care unit was 3 days (range, 2-7 days) compared with the median of 6 days (range, 2-34 days) obtained by the rest (P<.005). Duration of mechanical ventilation was 12 hours (range, 3-48 hours), and overall stay in the hospital was 6 days (range, 2-15 days) compared with 25 hours (range 6-432 hours) and 16 days (range, 4-50 days) obtained by the second group (P<.05). No complications were attributed to the use of the device. CONCLUSIONS: Monitoring by femoral arterial thermodilution has been feasible in our experience. Maintenance of a CI of 3 L min(-1) m(-2) or greater is related to a better patient's early outcome.

Continuous terlipressin infusion as rescue treatment in a case series of children with refractory septic shock.

BACKGROUND: Despite intensive therapy, refractory pediatric septic shock has a high rate of morbidity and mortality. Additional treatments are needed to improve outcomes in such cases. OBJECTIVE: To report the clinical effects of continuous terlipressin infusion as rescue treatment for children with septic shock refractory to high catecholamine doses. METHODS: Sixteen episodes of catecholamine-resistant septic shock were recorded in 15 children (aged from newborn to 15 years) who received compassionate rescue treatment with terlipressin at 6 pediatric intensive care units. Terlipressin treatment consisted of a loading dose (20 µg/kg) followed by continuous infusion at a rate of 4-20 µg/kg/h. Terlipressin was titrated at increases of 1 µg/kg/h to maintain mean arterial pressure (MAP) in normal range for age and to reduce catecholamine dosage. The main outcome was survival of the episode. Secondary outcomes included hemodynamic effects, ischemia, and terlipressin-related adverse events. RESULTS: Terlipressin increased median MAP from 48 (range 42-63) to 68 (45-115) mm Hg 30 minutes after terlipressin administration (p < 0.01). MAP was subsequently sustained, which allowed for the reduction of norepinephrine infusion from 2 µg/kg/min (1-4) at baseline to 1.5 µg/kg/min (0.4-4) at 1 hour, 1.3 µg/kg/min (0-8) at 4 hours, 1 µg/kg/min (0-2) at 12 hours, 0.45 µg/kg/min (0-1.4) at 24 hours, and 0 µg/kg/min (0-0.6) at 48 hours (p < 0.05 vs baseline in all cases). In 8 (50%) of the 16 septic shock episodes the patients survived, 7 (44%) without sequelae. One patient survived with sequelae (minor amputation and mild cutaneous ischemia). Eight patients had signs of ischemia at admission; terlipressin induced reversible ischemia in another 4 patients. Meningococcal infection, prior ischemia, and MAP were risk factors for mortality. CONCLUSIONS: Continuous terlipressin infusion may improve hemodynamics and survival in some children with refractory septic shock. Terlipressin could contribute to tissue ischemia.

Outbreak of vim-1-carbapenemase-producing Enterobacter cloacae in a pediatric intensive care unit.

Pediatric patients are rarely infected with metallo-ß-lactamase-producing Enterobacteriaceae. We describe 3 cases of children infected with VIM-1-producing clonal Enterobacter cloacae. Patients were treated with amikacin and cotrimoxazole. The blaVIM-1 gene was carried into a class 1 integron and an IncHI2 incompatibility group plasmid. Emergence of pediatric infections caused by carbapenemases-producing Enterobacteriaceae is a critical issue as they are resistant to most ß-lactam antibiotics.

Pediatric cardiac arrest refractory to advanced life support: is there a role for terlipressin?

OBJECTIVE: Pediatric cardiac arrest unresponsive to advanced life support and several adrenaline doses has a very poor prognosis. Alternative vasopressors could improve the results of resuscitation in such cases. We report our experience with the compassionate administration of terlipressin in children who suffered in-pediatric intensive care unit cardiac arrest and did not respond to immediate advanced life support and at least three epinephrine doses. DESIGN: Prospective multicenter registry. SETTING: Three pediatric intensive care units at university-affiliated tertiary care children's hospitals. PATIENTS: Five pediatric patients, aged 5 mos to 12 yrs, with in-pediatric intensive care unit cardiac arrest unresponsive to advanced life support that included at least three epinephrine doses. INTERVENTIONS: Addition of terlipressin (10-20 microg/kg intravenous, up to two doses) to standard cardiopulmonary resuscitation. MEASUREMENTS AND MAIN RESULTS: Sustained return of spontaneous circulation was achieved in four cases, two of them were declared dead 6 and 12 hrs later, and the remaining two survived without cardiopulmonary procedures-related sequelae and with good neurologic condition. CONCLUSIONS: Terlipressin might contribute to obtain sustained return of spontaneous circulation in children with refractory in-hospital cardiac arrest. A randomized controlled clinical trial should be conducted to investigate the optimal drug treatment in pediatric cardiac arrest.

Rescue treatment with terlipressin in children with refractory septic shock: a clinical study.

INTRODUCTION: Refractory septic shock has dismal prognosis despite aggressive therapy. The purpose of the present study is to report the effects of terlipressin (TP) as a rescue treatment in children with catecholamine refractory hypotensive septic shock. METHODS: We prospectively registered the children with severe septic shock and hypotension resistant to standard intensive care, including a high dose of catecholamines, who received compassionate therapy with TP in nine pediatric intensive care units in Spain, over a 12-month period. The TP dose was 0.02 mg/kg every four hours. RESULTS: Sixteen children (age range, 1 month-13 years) were included. The cause of sepsis was meningococcal in eight cases, Staphylococcus aureus in two cases, and unknown in six cases. At inclusion the median (range) Pediatric Logistic Organ Dysfunction score was 23.5 (12-52) and the median (range) Pediatric Risk of Mortality score was 24.5 (16-43). All children had been treated with a combination of at least two catecholamines at high dose rates. TP treatment induced a rapid and sustained improvement in the mean arterial blood pressure that allowed reduction of the catecholamine infusion rate after one hour in 14 out of 16 patients. The mean (range) arterial blood pressure 30 minutes after TP administration increased from 50.5 (37-93) to 77 (42-100) mmHg (P < 0.05). The noradrenaline infusion rate 24 hours after TP treatment decreased from 2 (1-4) to 1 (0-2.5) microg/kg/min (P < 0.05). Seven patients survived to the sepsis episode. The causes of death were refractory shock in three cases, withdrawal of therapy in two cases, refractory arrhythmia in three cases, and multiorgan failure in one case. Four of the survivors had sequelae: major amputations (lower limbs and hands) in one case, minor amputations (finger) in two cases, and minor neurological deficit in one case. CONCLUSION: TP is an effective vasopressor agent that could be an alternative or complementary therapy in children with refractory vasodilatory septic shock. The addition of TP to high doses of catecholamines, however, can induce excessive vasoconstriction. Additional studies are needed to define the safety profile and the clinical effectiveness of TP in children with septic shock.