Fluid bolus resuscitation with hypertonic saline albumin solution in critically ill children: a prospective observational pilot study.

To evaluate the hemodynamic effects and the safety profile of fluid bolus resuscitation with hypertonic saline albumin (HSA) in critically ill children, we performed a prospective observational pilot study between October 2018 and May 2021 in the pediatric intensive care unit (PICU) in a tertiary hospital in Madrid, Spain. Sixty-four HSA boluses were analyzed in 23 patients. A mean volume of 5.7 ml/kg (Standard Deviation, SD 2.3 ml/kg) per bolus was infused. Acute hypotension was the main indication. 91% of the patients had a cardiac disease, 56% of them had undergone cardiac surgery in the previous 72 h, and 47.8% associated right ventricular dysfunction. A significant increase in systolic, mean, and diastolic blood pressure and a decrease in the vasoactive index was observed after the infusion of HSA. This effect lasted for twenty-four hours (p < 0.05). Moreover, the amount of fluid requirements decreased significantly in the 6 h following HSA infusion [8.7 ml/kg (SD 9.6) vs. 15.1 ml/kg (SD 13.6) in the previous 6 h (p < 0.05)]. Serum levels of sodium and chloride increased after the infusion, reaching their peak concentration after one hour (143 mEq/L (SD 3.5) and 109.7 mEq/L (SD 6) respectively). HSA-related metabolic acidosis or acute kidney injury were not observed in this study. Hypertonic saline albumin is safe and effective when infused at a dose of 5 ml/kg in critically ill children. However, further research is required to confirm our findings.

Resuscitating the macro- vs. microcirculation in septic shock.

PURPOSE OF REVIEW: This review summarizes current literature about the relationships between macro and microcirculation and their practical clinical implications in children with septic shock. RECENT FINDINGS: Current evidence from experimental and clinical observational studies in children and adults with septic shock reveals that the response to treatment and resuscitation is widely variable. Furthermore, there is a loss of hemodynamic coherence, as resuscitation-induced improvement in macrocirculation (systemic hemodynamic parameters) does not necessarily result in a parallel improvement in the microcirculation. Therefore, patient-tailored monitoring is essential in order to adjust treatment requirements during resuscitation in septic shock. Optimal monitoring must integrate macrocirculation (heart rate, blood pressure, cardiac output, and ultrasound images), microcirculation (videomicroscopy parameters and capillary refill time) and cellular metabolism (lactic acid, central venous blood oxygen saturation, and difference of central venous to arterial carbon dioxide partial pressure). SUMMARY: There is a dire need for high-quality studies to assess the relationships between macrocirculation, microcirculation and tissue metabolism in children with septic shock. The development of reliable and readily available microcirculation and tissue perfusion biomarkers (other than lactic acid) is also necessary to improve monitoring and treatment adjustment in such patients.

Protocol for treatment of constipation with polyethylene glycol 3350 plus electrolytes in critically ill children.

INTRODUCTION AND OBJECTIVES: No studies have analysed the effectiveness of treatment for constipation in critically ill children. The aim of this study was to assess the implementation, efficacy and safety of a treatment protocol using polyethylene glycol 3350 with electrolytes (PEG 3350 + E) for constipation in critically ill children. METHODS: We conducted a single-centre prospective study in children admitted to the paediatric intensive care unit for a minimum of 72 h and who developed constipation. Children with previous gastrointestinal disorders or diseases were excluded. The patients were treated with rectal enemas or with the oral PEG 3350 + E protocol at the discretion of the treating physician. We compared clinical and demographic variables as well as adverse events (diarrhoea, abdominal distension and electrolyte imbalances). RESULTS: The sample included 56 patients with a mean age of 48.2 ±â€¯11.9 months, of who 55.4% were male. Forty-four patients (78.6%) were treated with PEG 3350 + E and 12 (21.4%) with rectal enemas. The proportion of patients that responded well to treatment was greater in the PEG 3350 + E group (79.5%) compared to the enema group (58.3%), but the difference was not statistically significant (P = .151). There were no significant differences between the groups in any of the adverse effects. Treatment with PEG 3350 + E was more effective in children aged less than 2 years (100%) compared to older children (100% vs 65.4%; P < .01), with no significant differences in the development of adverse events. CONCLUSIONS: The PEG 3350 + E treatment protocol for constipation in critically ill children was effective and associated with few adverse events, even in children aged less than 2 years.

Volumetric capnography and return of spontaneous circulation in an experimental model of pediatric asphyxial cardiac arrest.

A secondary analysis of a randomized study was performed to study the relationship between volumetric capnography (VCAP) and arterial CO2 partial pressure (PCO2) during cardiopulmonary resuscitation (CPR) and to analyze the ability of these parameters to predict the return of spontaneous circulation (ROSC) in a pediatric animal model of asphyxial cardiac arrest (CA). Asphyxial CA was induced by sedation, muscle relaxation and extubation. CPR was started 2 min after CA occurred. Airway management was performed with early endotracheal intubation or bag-mask ventilation, according to randomization group. CPR was continued until ROSC or 24 min of resuscitation. End-tidal carbon dioxide (EtCO2), CO2 production (VCO2), and EtCO2/VCO2/kg ratio were continuously recorded. Seventy-nine piglets were included, 26 (32.9%) of whom achieved ROSC. EtCO2 was the best predictor of ROSC (AUC 0.72, p < 0.01 and optimal cutoff point of 21.6 mmHg). No statistical differences were obtained regarding VCO2, VCO2/kg and EtCO2/VCO2/kg ratios. VCO2 and VCO2/kg showed an inverse correlation with PCO2, with a higher correlation coefficient as resuscitation progressed. EtCO2 also had an inverse correlation with PCO2 from minute 18 to 24 of resuscitation. Our findings suggest that EtCO2 is the best VCAP-derived parameter for predicting ROSC. EtCO2 and VCO2 showed an inverse correlation with PCO2. Therefore, these parameters are not adequate to measure ventilation during CPR.

Doppler ultrasound in the assessment of renal perfusion before and during continuous kidney replacement therapy in the pediatric intensive care unit.

BACKGROUND: This study aimed to assess observer variability and describe renal resistive index (RRI) and pulsatility index (PI) before and after onset of continuous kidney replacement therapy (CKRT). A secondary objective was to correlate Doppler ultrasound findings with those from direct measurement of renal blood flow (RBF). METHODS: This is a prospective observational study in hemodynamically stable Maryland piglets with and without acute kidney injury (AKI) and in hemodynamically unstable critically ill children requiring CKRT. Doppler-based RRI and PI were assessed for each subject. Measurements were made by two different operators (pediatric intensivists) before and after CKRT onset. RESULTS: Observer variability assessment in the measurement of RRI and PI rendered a moderate correlation for both RRI (ICC 0.65, IQR 0.51-0.76) and PI (ICC 0.63, IQR 0.47-0.75). RRI and PI showed no correlation with RBF or urine output. Baseline RRI and PI were normal in control piglets [RRI 0.68 (SD 0.02), PI 1.25 (SD 0.09)] and those with AKI [RRI 0.68 (SD 0.03), PI 1.20 (SD 0.13)]. Baseline RRI and PI were elevated in critically ill children (RRI 0.85, PI 2.0). PI and RRI did not change with CKRT in any study group. CONCLUSIONS: Observer variability between inexperienced pediatric intensivists was comparable with that between senior and junior operators. Doppler-based calculations did not correlate with invasive measurements of RBF. RRI and PI were normal in hemodynamically stable piglets with and without AKI. RRI and PI were high in hemodynamically unstable patients requiring CKRT. RRI and PI did not change after CKRT onset, despite changes in hemodynamic status. A higher resolution version of the Graphical abstract is available as Supplementary information.

Effects of airway management and tidal volume feedback ventilation during pediatric resuscitation in piglets with asphyxial cardiac arrest.

To compare the effect on the recovery of spontaneous circulation (ROSC) of early endotracheal intubation (ETI) versus bag-mask ventilation (BMV), and expiratory real-time tidal volume (VTe) feedback (TVF) ventilation versus without feedback or standard ventilation (SV) in a pediatric animal model of asphyxial cardiac arrest. Piglets were randomized into five groups: 1: ETI and TVF ventilation (10 ml/kg); 2: ETI and TVF (7 ml/kg); 3: ETI and SV; 4: BMV and TVF (10 ml/kg) and 5: BMV and SV. Thirty breaths-per-minute guided by metronome were given. ROSC, pCO2, pO2, EtCO2 and VTe were compared among groups. Seventy-nine piglets (11.3 ± 1.2 kg) were included. Twenty-six (32.9%) achieved ROSC. Survival was non-significantly higher in ETI (40.4%) than BMV groups (21.9%), p = 0.08. No differences in ROSC were found between TVF and SV groups (30.0% versus 34.7%, p = 0.67). ETI groups presented lower pCO2, and higher pO2, EtCO2 and VTe than BMV groups (p < 0.05). VTe was lower in TVF than in SV groups and in BMV than in ETI groups (p < 0.05). Groups 1 and 3 showed higher pO2 and lower pCO2 over time, although with hyperventilation values (pCO2 < 35 mmHg). ETI groups had non significantly higher survival rate than BMV groups. Compared to BMV groups, ETI groups achieved better oxygenation and ventilation parameters. VTe was lower in both TVF and BMV groups. Hyperventilation was observed in intubated animals with SV and with 10 ml/kg VTF.

Hemodynamic disturbances and oliguria during continuous kidney replacement therapy in critically ill children.

BACKGROUND: About 1.5% of patients admitted to the Pediatric Intensive Care Unit (PICU) will require continuous kidney replacement therapy (CKRT)/renal replacement therapy (CRRT). Mortality of these patients ranges from 30 to 60%. CKRT-related hypotension (CKRT-RHI) can occur in 19-45% of patients. Oliguria after onset of CKRT is also common, but to date has not been addressed directly in the scientific literature. METHODS: A prospective observational study was conducted to define factors involved in the hemodynamic changes that take place during the first hours of CKRT, and their relationship with urinary output. RESULTS: Twenty-five patients who were admitted to a single-center PICU requiring CKRT between January 1, 2014, and December 31, 2018, were included, of whom 56.3% developed CKRT-RHI. This drop in blood pressure was transient and rapidly restored to baseline, and significantly improved after the third hour of CKRT, as core temperature and heart rate decreased. Urine output significantly decreased after starting CKRT, and 72% of patients were oliguric after 6 h of therapy. Duration of CKRT was significantly longer in patients presenting with oliguria than in non-oliguric patients (28.7 vs. 7.9 days, p = 0.013). CONCLUSIONS: The initiation of CKRT caused hemodynamic instability immediately after initial connection in most patients, but had a beneficial effect on the patient's hemodynamic status after 3 h of therapy, presumably owing to decreases in body temperature and heart rate. Urine output significantly decreased in all patients and was not related to negative fluid balance, patient's hemodynamic status, CKRT settings, or kidney function parameters.

Evaluation of the pediatric life support instructors courses.

OBJECTIVE: To evaluate the results and quality of pediatric cardiopulmonary resuscitation (CPR) instructor training courses. METHODS: A retrospective analysis was performed of the results of 24 pediatric CPR instructor courses held over 21 years (1999 to 2019). The results of participants' evaluation of theory and practice sessions were analyzed. In addition, participants were asked to answer an anonymous survey to assess their opinion on the quality of theory and practice lessons, course organization and methodology, and instructor training. The results were compared by professional groups. RESULTS: A total of 560 participants completed the instructor course. Of them, 554 passed theory and practice tests (98.9 %). The mean score obtained in theory tests was 9.2 (0.8) out of 10. The mean score obtained in all practice tests was > 3.5 out of 5. Participants evaluated all the aspects of the course (theory and practice content, organization, teaching methodology, and instructors) with mean scores over 8 out of 10. CONCLUSIONS: Specific pediatric and neonatal CPR instructor courses are a cornerstone in the process of CPR training and ensuring the homogeneity and quality of training. Most of the participants obtained the qualification of instructors and their evaluation of the course was very positive.

Cooperation program for volunteer medical students for training in pediatric cardiopulmonary resuscitation and accident prevention in Honduras.

OBJECTIVES: To analyze a training program in accident prevention and care and Pediatric Basic Cardiopulmonary Resuscitation taught by medical students. RESULTS: Medical students were trained as instructors. Four courses of were launched in Honduras, and the results were analyzed through a theoretical and practical evaluation and an anonymous survey. The volunteer experience for the students and the benefits to the population were positively valued. 37 students received the training. The score in the initial theoretical evaluation was 5.9 of 17 and in the final 10.5, p < 0.001. 89.1% and 91.9% of the students achieved adequate practical learning in basic Cardiopulmonary Resuscitation for children and infants respectively. The course was rated excellently by the students. We conclude that a training program in accident prevention and care and Pediatric Basic Cardiopulmonary Resuscitation taught by medical students could be useful in a cooperation health program.

Comparison of the effect of three different protein content enteral diets on serum levels of proteins, nitrogen balance, and energy expenditure in critically ill infants: study protocol for a randomized controlled trial.

BACKGROUND: Nutritional support is essential in the care of critically ill children since malnutrition in this population is associated with increased morbidity and mortality. Injury in patients admitted to pediatric intensive care units (PICU) results in a catabolic state and augmented protein breakdown, leading to a negative protein balance. Current recommendations about protein prescription in the PICU are fundamentally based on expert opinions, and the minimum threshold is 1.5 g/kg per day of protein, although protein needs could be higher in certain subgroups of patients. The main objectives of the present study are to examine whether the administration of a protein-enriched infant formula increases the serum levels of total proteins, albumin, prealbumin, transferrin, and retinol and improves nitrogen balance and to analyze the effect of the high-protein diet on energy expenditure. A secondary objective is to register possible secondary effects of the protein-enriched diet. METHODS: A multicenter prospective randomized controlled trial (RCT) will be performed in three hospitals. Patients meeting inclusion criteria will be randomly allocated to one of three enteral feeding formulae with different protein contents. Blood and urine test, nitrogen balance assessment, and energy expenditure testing by indirect calorimetry will be performed at the beginning of the nutrition regimen and at 24 h, 72 h and 5-7 days after initiation. The sample size for this trial is estimated to be 90 participants (about 30 participants in each group). The data analysis will be by intention to treat. DISCUSSION: This RCT will provide new data about the amount of protein needed to improve levels of serum protein and nitrogen balance, a surrogate of protein balance, in critically ill infants receiving enteral nutrition. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03901742 . Registered April 1, 2019 - Retrospectively registered.

Microcirculatory Differences in Children With Congenital Heart Disease According to Cyanosis and Age.

Background: Congenital heart disease (CHD) is one of the main causes of morbidity and mortality in children. Microcirculatory changes in CHD patients have previously been investigated using a variety of techniques. Handheld videomicroscopy enables non-invasive direct visualization of the microcirculatory bed. The aim of our study was to determine if there are microcirculatory differences among CHD patients based on age and the presence of cyanosis. Methods: A prospective observational study was carried out. Patients with CHD undergoing corrective surgery were evaluated after anesthetic induction prior to surgery. Microcirculation was evaluated using sidestream dark field (SDF) imaging. Hemodynamics and respiratory, biochemical, and tissue perfusion parameters were analyzed. Results: A total of 30 patients were included, of whom 14 were classified as cyanotic and 16 as non-cyanotic. Cyanotic patients had a higher total vessel density (TVD) (p = 0.016), small vessel density (p = 0.004), and perfused small vessel density (p = 0.013), while their microvascular flow index (MFI) was lower (p = 0.013). After adjustment for age and PaO2, cyanotic patients showed increased TVD (p = 0.023), and small vessel density (p = 0.025) compared to non-cyanotic patients but there were no differences on the MFI. Age was directly correlated with total MFI (spearman's rho = 0.499, p = 0.005) and small vessel MFI (spearman's rho = 0.420, p = 0.021). After adjustment for the type of CHD (cyanotic vs. non-cyanotic) patients with MFI and small MFI vessels <3 were younger than those with values ≥3 (p = 0.033 and p = 0.037). Conclusions: SDF-based evaluation of microcirculation in CHD patients showed that patients with cyanotic defects had higher vascular density, as compared to patients with non-cyanotic defects. Younger patients were more likely to have a low MFI regardless of their type of CHD.

Comparison between synchronized and non-synchronized ventilation and between guided and non-guided chest compressions during resuscitation in a pediatric animal model after asphyxial cardiac arrest.

INTRODUCTION: There are no studies comparing synchronized and non-synchronized ventilation with bag-valve mask ventilation (BVMV) during cardiopulmonary resuscitation (CPR) in pediatric patients. The main aim is to compare between synchronized and non-synchronized BVMV with chest compressions (CC), and between guided and non-guided CC with a real-time feedback-device in a pediatric animal model of asphyxial cardiac arrest (CA). The secondary aim is to analyze the quality of CC during resuscitation. METHODS: 60 piglets were randomized for CPR into four groups: Group A: guided-CC and synchronized ventilation; Group B: guided-CC and non-synchronized ventilation; Group C: non-guided CC and synchronized ventilation; Group D: non-guided CC and non-synchronized ventilation. Return of spontaneous circulation (ROSC), hemodynamic and respiratory parameters, and quality of CC were compared between all groups. RESULTS: 60 piglets were included. Twenty-six (46.5%) achieved ROSC: A (46.7%), B (66.7%), C (26.7%) and D (33.3%). Survival rates were higher in group B than in groups A+C+D (66.7% vs 35.6%, p = 0.035). ROSC was higher with guided-CC (A+B 56.7% vs C+D 30%, p = 0.037). Piglets receiving non-synchronized ventilation did not show different rates of ROSC than synchronized ventilation (B+D 50% vs A+C 36.7%, p = 0.297). Non-synchronized groups showed lower arterial pCO2 after 3 minutes of CPR than synchronized groups: 57 vs 71 mmHg, p = 0.019. No differences were found in arterial pH and pO2, mean arterial pressure (MAP) or cerebral blood flow between groups. Chest compressions were shallower in surviving than in non-surviving piglets (4.7 vs 5.1 cm, p = 0.047). There was a negative correlation between time without CC and MAP (r = -0.35, p = 0.038). CONCLUSIONS: The group receiving non-synchronized ventilation and guided-CC obtained significantly higher ROSC rates than the other modalities of resuscitation. Guided-CC achieved higher ROSC rates than non-guided CC. Non-synchronized ventilation was associated with better ventilation parameters, with no differences in hemodynamics or cerebral flow.

Hemodynamic impact of the connection to continuous renal replacement therapy in critically ill children.

BACKGROUND: Continuous renal replacement therapy (CRRT) is the treatment of choice for critically ill children with acute kidney injury. Hypotension after starting CRRT is frequent but very few studies have analyzed its incidence and clinical relevance. METHODS: A prospective, observational study was performed including critically ill children treated with CRRT between 2010 and 2014. Hemodynamic data and connection characteristics were collected before, during, and 60 min after CRRT circuit connection. Hypotension with the connection was defined as a decrease in > 20% of the mean arterial pressure from baseline or when intravenous fluid resuscitation or an increase in vasopressors was required. RESULTS: One hundred sixty-one connections in 36 children (median age 18.8 months) were analyzed. Twenty-eight patients (77.8%) were in the postoperative period of cardiac surgery, 94% had mechanical ventilation, and 86.1% had vasopressors. The heparinized circuit priming solution was discarded in 8.7% and infused to the patient in 18% of the connections. The circuit was re-primed in the remaining 73.3% using albumin (79.3%), red blood cells (4.5%), or another crystalloid solution without heparin (16.2%). Hypotension occurred in 49.7% of the connections a median of 5 min after the beginning of the therapy. Fluid resuscitation was required in 38.5% and the dose of vasopressors was increased in 12.4% of the connections. There was no relationship between hypotension and age or weight. Re-priming the circuit with albumin reduced the incidence of hypotension from 71.4 to 44.6% (p = 0.004). CONCLUSIONS: Hypotension after the connection to CRRT is very frequent in critically ill children. Re-priming the circuit with albumin could improve hemodynamics during connection.

Correction: Cisplatin-Induced Non-Oliguric Acute Kidney Injury in a Pediatric Experimental Animal Model in Piglets.

[This corrects the article DOI: 10.1371/journal.pone.0149013.].

Hemodynamic Effects of Connection to Continuous Renal Replacement Therapy in a Pediatric Animal Model.

To assess the hemodynamic effects of connection to continuous renal replacement therapy (CRRT) in a pediatric experimental animal model. Prospective experimental study was performed using piglets between 2 and 3 months of age and 9-11 kg. CRRT with a PrismaflexR monitor and HF20 filter (surface of 0.2 m2 ) was started after monitoring and anesthetic induction with an initial blood flow at 20 mL/min with 10 mL/min increases every minute until the goal flow of 5 mL/kg/min was achieved. Heart rate, blood pressure, central venous pressure, cardiac index, and renal blood flow were registered at baseline, 5, 15, 30, 60, 120, 180, 240, and 360 min. IBM SPSS Statistics 20.0 package was used for analysis. A P value of <0.05 was considered statistically significant. Thirty-four piglets were studied. Blood pressure, cardiac output, and systemic vascular resistance significantly decreased 5-min after CRRT connection (mean arterial pressure from 85.5 to 70.8 mm Hg, P < 0.001, cardiac index from 3.6 to 3.3 L/min/m2 P = 0.024, and systemic vascular resistance index from 1759 to 1607 dyn.s/cm5 P = 0.012). No significant changes were found in renal blood flow or central venous pressure. All parameters gradually increased at 15 and 30 min after connection but complete recovery was never achieved. Connection to CRRT produces a significant decrease in arterial pressure, cardiac index, and peripheral vascular resistances in hemodynamically stable piglets.

Comparison between manual and mechanical chest compressions during resuscitation in a pediatric animal model of asphyxial cardiac arrest.

AIMS: Chest compressions (CC) during cardiopulmonary resuscitation are not sufficiently effective in many circumstances. Mechanical CC could be more effective than manual CC, but there are no studies comparing both techniques in children. The objective of this study was to compare the effectiveness of manual and mechanical chest compressions with Thumper device in a pediatric cardiac arrest animal model. MATERIAL AND METHODS: An experimental model of asphyxial cardiac arrest (CA) in 50 piglets (mean weight 9.6 kg) was used. Animals were randomized to receive either manual CC or mechanical CC using a pediatric piston chest compressions device (Life-Stat®, Michigan Instruments). Mean arterial pressure (MAP), arterial blood gases and end-tidal CO2 (etCO2) values were measured at 3, 9, 18 and 24 minutes after the beginning of resuscitation. RESULTS: There were no significant differences in MAP, DAP, arterial blood gases and etCO2 between chest compression techniques during CPR. Survival rate was higher in the manual CC (15 of 30 = 50%) than in the mechanical CC group (3 of 20 = 15%) p = 0.016. In the mechanical CC group there was a non significant higher incidence of haemorrhage through the endotracheal tube (45% vs 20%, p = 0.114). CONCLUSIONS: In a pediatric animal model of cardiac arrest, mechanical piston chest compressions produced lower survival rates than manual chest compressions, without any differences in hemodynamic and respiratory parameters.

Ventilation during cardiopulmonary resuscitation in children: a survey on clinical practice.

BACKGROUND: This study aimed to investigate the ventilation practice during cardiopulmonary resuscitation (CPR) and after return of spontaneous circulation (ROSC) in children. METHODS: An online survey of CPR practices was designed and sent to healthcare professionals treating children. RESULTS: A total of 477 healthcare professionals from 46 countries responded to this survey; 92.7% were physicians and 64.2% worked in pediatric intensive care units. Specific CPR guidelines were used by 97.7% of respondents. The respiratory rate most frequently used for children over 12 months was 13 to 20 respirations per minute (rpm) (46% in intubated and 41.8% in non-intubated). For infants under 12 months, the most frequently used respiratory rate was 21 to 30 rpm in intubated patients (37.3%): in non-intubated infants, 13 to 20 rpm (26.5%) and 21 to 30 rpm (26.5%) were used with the same frequency. In North America, the respiratory rate most widely used was 7 to 12 rpm; higher rates (13 to 20 rpm and 21 to 30 rpm) were used in Europe and Latin America (P<0.001). After ROSC, no significant differences in the respiratory rates used were found between the continents. More than 40% of healthcare professionals had a target oxygen saturation below 94%; more than 10% used a target arterial PCO2 below 35 mmHg and more than 13% above 45 mmHg. CONCLUSIONS: There is considerable variation in the management of ventilation of children in cardiac arrest, and international recommendations are not being followed in a high percentage of cases.