Jimena del Castillo

Hyperoxia, hypocapnia and hypercapnia as outcome factors after cardiac arrest in children

PURPOSE Arterial hyperoxia after resuscitation has been associated with increased mortality in adults. The aim of this study was to test the hypothesis that post-resuscitation hyperoxia and hypocapnia are associated with increased mortality after resuscitation in pediatric patients. METHODS We performed a prospective observational multicenter hospital-based study including 223 children aged between 1 month and 18 years who achieved return of spontaneous circulation after in-hospital cardiac arrest and for whom arterial blood gas analysis data were available. RESULTS After return of spontaneous circulation, 8.5% of patients had hyperoxia (defined as PaO(2)>300 mm Hg) and 26.5% hypoxia (defined as PaO(2)<60 mm Hg). No statistical differences in mortality were observed when patients with hyperoxia (52.6%), hypoxia (42.4%), or normoxia (40.7%) (p=0.61). Hypocapnia (defined as PaCO(2)<30 mm Hg) was observed in 13.5% of patients and hypercapnia (defined as PaCO(2)>50 mm Hg) in 27.6%. Patients with hypercapnia or hypocapnia had significantly higher mortality (59.0% and 50.0%, respectively) than patients with normocapnia (33.1%) (p=0.002). At 24h after return of spontaneous circulation, neither PaO(2) nor PaCO(2) values were associated with mortality. Multiple logistic regression analysis showed that hypercapnia (OR, 3.27; 95% CI, 1.62-6.61; p=0.001) and hypocapnia (OR, 2.71; 95% CI, 1.04-7.05; p=0.04) after return of spontaneous circulation were significant mortality factors. CONCLUSIONS In children resuscitated from cardiac arrest, hyperoxemia after return of spontaneous circulation or 24h later was not associated with mortality. On the other hand, hypercapnia and hypocapnia were associated with higher mortality than normocapnia.

The use of continuous renal replacement therapy in series with extracorporeal membrane oxygenation

A large percentage of patients on extracorporeal membrane oxygenation (ECMO) require continuous renal replacement therapy (CRRT) usually performed through a different venous access or by introducing a filter into the ECMO circuit. Here, we evaluated the efficacy and safety of including a CRRT machine in the circuit by connecting its inlet line after the centrifugal pump and its outlet line before the oxygenator. We tested the function of the combined system initially in a closed circuit, followed by an experimental animal study, and, finally, in a clinical trial with six children. Both machines functioned adequately and there were no significant changes in the pressures of the ECMO circuit after the introduction of the CRRT device, thus achieving the preset negative balances and normalization of the serum urea and creatinine concentrations. The mean life of the filters was about 138 h, and only one filter needed changing due to clotting. Our study shows that the introduction of a CRRT device into the ECMO circuit is a safe and effective technique that improves fluid balance, increases filter life, and does not cause complications. For these reasons, this may be a good method for performing CRRT in patients on ECMO.

Helicobacter pylori stimulates pepsinogen secretion from isolated human peptic cells

Background: Different acid and peptic related gastroduodenal diseases are associated with both increased gastric secretion and Helicobacter pylori infection. Patients with H pylori associated gastritis or duodenal ulcer have increased serum pepsinogen levels which decrease after eradication. The mechanisms of H pylori induced gastric mucosal damage are not completely understood. Aim: To determine the effects of H pylori on pepsinogen secretion from isolated human peptic cells. Methods: Dispersed human peptic cells were prepared from endoscopically obtained biopsy specimens after collagenase digestion, mechanical disruption, and density gradient centrifugation. H pylori was obtained from gastric biopsies (antrum and body), and cultured in non-selective and selective media. Isolates of H pylori were used at different concentrations (1–20×106 colony forming units (cfu)). Results: H pylori (106–2×107 cfu) increased basal pepsinogen secretion in a concentration dependent manner. This stimulus was not observed with Escherichia coli. The increased secretion was in addition to that observed with 0.1 mM histamine and 0.1 mM dibutyryl-cyclic adenosine monophosphate. However, H pylori did not affect either carbamylcholine (0.1–10 μM) or cholecystokinin (1 μM) stimulated pepsinogen secretion. Addition of the nitric oxide synthase inhibitor Nw-monomethyl-l-arginine (1 mM) inhibited H pylori induced cGMP generation and pepsinogen secretion, which were also reduced in the absence of extracellular calcium. H pylori induced pepsinogen secretion was not affected by the absence/presence of the cagA gene. Conclusions: H pylori increases pepsinogen secretion from human peptic cells through a calcium and nitric oxide mediated intracellular pathway. This effect is independent of the H pylori virulent cagA gene, and may be a mechanism of H pylori induced gastric mucosal damage.

Hypophosphatemia and phosphate supplementation during continuous renal replacement therapy in children

Severe hypophosphatemia can cause generalized muscle weakness, paralysis of the respiratory muscles, myocardial dysfunction, reduced peripheral vascular resistance, and encephalopathy. Here we conducted a prospective study to determine the incidence of hypophosphatemia in 47 children on continuous renal replacement therapy and to evaluate the efficacy and safety of adding phosphate to the replacement and dialysate solutions of 38 pediatric patients. During continuous renal replacement therapy, 68% of patients were found to have hypophosphatemia, significantly more than the 12% of patients at the beginning of therapy. There was no higher incidence of hypophosphatemia among patients requiring insulin, diuretics, parenteral nutrition, or high doses of vasoactive drugs. In the children to whom phosphate was not added to replacement and dialysate solutions, 85% presented with an incidence of hypophosphatemia and 36% required intravenous phosphate replacement, rates significantly higher than in those patients where phosphate was added to the solutions. Phosphate supplementation did not cause any instability of the mixtures or other complications. We show here that the incidence of hypophosphatemia in children on continuous renal replacement therapy is very high. Further, we show that the addition of phosphate to replacement and dialysate solutions is safe and that it reduces the incidence of hypophosphatemia and the need for intravenous phosphate treatment.

Complications of continuous renal replacement therapy in critically ill children: a prospective observational evaluation study

IntroductionContinuous renal replacement therapy (CRRT) frequently gives rise to complications in critically ill children. However, no studies have analyzed these complications prospectively. The purpose of this study was to analyze the complications of CRRT in children and to study the associated risk factors.MethodsA prospective, single-centre, observational study was performed in all critically ill children treated using CRRT in order to determine the incidence of complications related to the technique (problems of catheterization, hypotension at the time of connection to the CRRT, hemorrhage, electrolyte disturbances) and their relationship with patient characteristics, clinical severity, need for vasoactive drugs and mechanical ventilation, and the characteristics of the filtration techniques.ResultsOf 174 children treated with CRRT, 13 (7.4%) presented problems of venous catheterization; this complication was significantly more common in children under 12 months of age and in those weighing less than 10 kg. Hypotension on connection to CRRT was detected in 53 patients (30.4%). Hypotension was not associated with any patient or CRRT characteristics. Clinically significant hemorrhage occurred in 18 patients (10.3%); this complication was not related to any of the variables studied. The sodium, chloride, and phosphate levels fell during the first 72 hours of CRRT; the changes in electrolyte levels during the course of treatment were not found to be related to any of the variables analyzed, nor were they associated with mortality.ConclusionsCRRT-related complications are common in children and some are potentially serious. The most common are hypotension at the time of connection and electrolyte disturbances. Strict control and continuous monitoring of the technique are therefore necessary in children on CRRT.

Circuit life span in critically ill children on continuous renal replacement treatment: a prospective observational evaluation study.

IntroductionOne of the greatest problems with continuous renal replacement therapy (CRRT) is early coagulation of the filters. Few studies have monitored circuit function prospectively. The purpose of this study was to determine the variables associated with circuit life in critically ill children with CRRT.MethodsA prospective observational study was performed in 122 children treated with CRRT in a pediatric intensive care unit from 1996 to 2006. Patient and filter characteristics were analyzed to determine their influence on circuit life. Data were collected on 540 filters in 122 patients and an analysis was performed of the 365 filters (67.6%) that were changed due to circuit coagulation.ResultsThe median circuit life was 31 hours (range 1 to 293 hours). A univariate and multivariate logistic regression study was performed to assess the influence of each one of the factors on circuit life span. No significant differences in filter life were found according to age, weight, diagnoses, pump, site of venous access, blood flow rate, ultrafiltration rate, inotropic drug support, or patient outcome. The mean circuit life span was longer when the heparin dose was greater than 20 U/kg per hour (39 versus 29.1 hours; P = 0.008), with hemodiafiltration compared with hemofiltration (34 versus 22.7 hours; P = 0.001), with filters with surface areas of 0.4 to 0.9 m2 (38.2 versus 26.1 hours; P = 0.01), and with a catheter size of 6.5 French or greater (33.0 versus 25.0 hours; P = 0.04). In the multivariate analysis, hemodiafiltration, heparin dose of greater than 20 U/kg per hour, filter surface area of 0.4 m2 or greater, and initial creatinine of less than 2 mg/dL were associated with a filter life of more than 24 and 48 hours. Total effluent rate of greater than 35 mL/kg per hour was associated only with a filter life of more than 24 hours.ConclusionCircuit life span in CRRT in children is short but may be increased by the use of hemodiafiltration, higher heparin doses, and filters with a high surface area.

Shockable rhythms and defibrillation during in-hospital pediatric cardiac arrest

OBJECTIVE To analyze the results of cardiopulmonary resuscitation (CPR) that included defibrillation during in-hospital cardiac arrest (IH-CA) in children. METHODS A prospective multicenter, international, observational study on pediatric IH-CA in 12 European and Latin American countries, during 24 months. Data from 502 children between 1 month and 18 years were collected using the Utstein template. Patients with a shockable rhythm that was treated by electric shock(s) were included. The primary endpoint was survival at hospital discharge. Univariate logistic regression analysis was performed to find outcome factors. RESULTS Forty events in 37 children (mean age 48 months, IQR: 7-15 months) were analyzed. An underlying disease was present in 81.1% of cases and 24.3% had a previous CA. The main cause of arrest was a cardiac disease (56.8%). In 17 episodes (42.5%) ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) was the first documented rhythm, and in 23 (57.5%) it developed during CPR efforts. In 11 patients (27.5%) three or more shocks were needed to achieve defibrillation. Return of spontaneous circulation (ROSC) was obtained in 25 cases (62.5%), that was sustained in 20 (50.0%); however only 12 children (32.4%) survived to hospital discharge. Children with VF/pVT as first documented rhythm had better sustained ROSC (64.7% vs. 39.1%, p=0.046) and survival to hospital discharge rates (58.8% vs. 21.7%, p=0.02) than those with subsequent VF/pVT. Survival rate was inversely related to duration of CPR. Clinical outcome was not related to the cause or location of arrest, type of defibrillator and waveform, energy dose per shock, number of shocks, or cumulative energy dose, although there was a trend to better survival with higher doses per shock (25.0% with <2Jkg(-1), 43.4% with 2-4Jkg(-1) and 50.0% with >4Jkg(-1)) and worse with higher number of shocks and cumulative energy dose. CONCLUSION The termination of pediatric VF/pVT in the IH-CA setting is achieved in a low percentage of instances with one electrical shock at 4Jkg(-1). When VF/pVT is the first documented rhythm, the results of defibrillation are better than in the case of subsequent VF/pVT. No clear relationship between defibrillation protocol and ROSC or survival has been observed. The optimal pediatric defibrillation dose remains to be determined; therefore current resuscitation guidelines cannot be considered evidence-based, and additional research is needed.

Cardiac arrest and resuscitation in the pediatric intensive care unit: a prospective multicenter multinational study.

OBJECTIVE The aim of the study was to analyze the mortality and neurological outcome factors of in-pediatric intensive care unit (in-PICU) cardiac arrest (CA) in a multicenter international study. PATIENTS AND METHODS It was a prospective observational multicenter study in Latin-American countries, Spain, Portugal, and Italy. A total of 250 children aged from 1 month to 18 years who suffered in-PICU CA were studied. Countries and patient-related variables, arrest life, support-related variables, procedures, and clinical and neurological status at hospital discharge according to the Pediatric Cerebral Performance Category (PCPC) scale were registered. The primary endpoint was survival at hospital discharge and neurological outcome at the same time was the secondary endpoint. Univariate and multivariate logistic regression analyses were performed. RESULTS Return of spontaneous circulation maintained longer than 20 min was achieved in 172 patients (69.1%) and 101 (40.4%) survived to hospital discharge. In the univariate analysis, oncohematologic diseases, inotropic infusion at the time of CA, sepsis and neurologic causes of CA, primary cardiac arrest, need of adrenaline, bicarbonate or volume expansion during resuscitation, and long duration of resuscitation were related with mortality. In the multivariate logistic regression analysis, factors related to mortality were hemato-oncologic illness and previous treatment with vasoactive drugs at the time of CA event, neurological etiology of CA, and cardiopulmonary resuscitation (CPR) duration for more than 10 min. One year after CA, neurological status was assessed in 65 patients; among them, 81.5% had mild disabilities or none. CONCLUSIONS Survival with good neurological outcome of CA in the PICU is improving. The most important prognostic indicator is the duration of resuscitation.

High-Flow Oxygen Therapy: Pressure Analysis in a Pediatric Airway Model

BACKGROUND: The mechanism of high-flow oxygen therapy and the pressures reached in the airway have not been defined. We hypothesized that the flow would generate a low continuous positive pressure, and that elevated flow rates in this model could produce moderate pressures. The objective of this study was to analyze the pressure generated by a high-flow oxygen therapy system in an experimental model of the pediatric airway. METHODS: An experimental in vitro study was performed. A high-flow oxygen therapy system was connected to 3 types of interface (nasal cannulae, nasal mask, and oronasal mask) and applied to 2 types of pediatric manikin (infant and neonatal). The pressures generated in the circuit, in the airway, and in the pharynx were measured at different flow rates (5, 10, 15, and 20 L/min). The experiment was conducted with and without a leak (mouth sealed and unsealed). Linear regression analyses were performed for each set of measurements. RESULTS: The pressures generated with the different interfaces were very similar. The maximum pressure recorded was 4 cm H2O with a flow of 20 L/min via nasal cannulae or nasal mask. When the mouth of the manikin was held open, the pressures reached in the airway and pharynxes were undetectable. Linear regression analyses showed a similar linear relationship between flow and pressures measured in the pharynx (pressure = −0.375 + 0.138 × flow) and in the airway (pressure = −0.375 + 0.158 × flow) with the closed mouth condition. CONCLUSIONS: According to our hypothesis, high-flow oxygen therapy systems produced a low-level CPAP in an experimental pediatric model, even with the use of very high flow rates. Linear regression analyses showed similar linear relationships between flow and pressures measured in the pharynx and in the airway. This finding suggests that, at least in part, the effects may be due to other mechanisms.

Long-term evolution after in-hospital cardiac arrest in children: Prospective multicenter multinational study☆

OBJECTIVE The main objective was to study survival and neurologic evolution of children who suffered in-hospital pediatric cardiac arrest (CA). The secondary objective was to analyze the influence of risk factors on the long term outcome after CA. METHODS prospective, international, observational, multicentric study in 48 hospitals of 12 countries. CA in children between 1 month and 18 years were analyzed using the Utstein template. Survival and neurological state measured by Pediatric Cerebral Performance Category (PCPC) scale one year after hospital discharge was evaluated. RESULTS 502 patients with in-hospital CA were evaluated. 197 of them (39.2%) survived to hospital discharge. PCPC at hospital discharge was available in 156 of survivors (79.2%). 76.9% had good neurologic state (PCPC 1-2) and 23.1% poor PCPC values (3-6). One year after cardiac arrest we could obtain data from 144 patients (28.6%). PCPC was available in 116 patients. 88 (75.9%) had a good neurologic evaluation and 28 (24.1%) a poor one. A neurological deterioration evaluated by PCPC scale was observed in 40 patients (7.9%). One year after cardiac arrest PCPC scores compared to hospital discharge had worsen in 7 patients (6%), remained constant in 103 patients (88.8%) and had improved in 6 patients (5.2%). CONCLUSION Survival one year after cardiac arrest in children after in-hospital cardiac arrest is high. Neurologic outcome of these children a year after cardiac arrest is mostly the same as after hospital discharge. The factors associated with a worst long-term neurological outcome are the etiology of arrest being a traumatic or neurologic illness, and the persistency of higher lactic acid values 24h after ROSC. A standardised basic protocol even practicable for lower developed countries would be a first step for the new multicenter studies.