Routine laboratory measures of heparin anticoagulation for children on extracorporeal membrane oxygenation: Systematic review and meta-analysis.

OBJECTIVE: Specific protocols for anticoagulation for children on ECMO vary across institutions, with most using a continuous infusion of unfractionated heparin. The goal of this study is to aid clinician's decision on the best measure of heparin anticoagulation test; which would be the one that correlates well with heparin activity and helps in predicting hemorrhagic and thrombotic complications. DATA SOURCES: A comprehensive search of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Scopus was conducted from each database's inception to 07/13/2018. STUDY SELECTION: Studies evaluating children (<18 years) treated with ECMO and evaluating ACT, aPTT, TEG and Anti-Xa in any language were included. DATA EXTRACTION: Two reviewers selected and appraised studies independently, and abstracted data. RESULTS: We included 19 studies (759 patients, mean age 19.8 months). Meta-analysis showed strong correlation between heparin dosing and anti-Xa. Additionally, there was not a strong correlation between laboratory tests and complications (hemorrhagic and thrombosis), or mortality. CONCLUSION: Based on current evidence, Anti-Xa is the only laboratory test that shows strong correlation with heparin infusion dose and seems like the most suitable test for monitoring of anticoagulation with heparin in children on ECMO.

Adult extracorporeal membrane oxygenation: an international survey of transfusion and anticoagulation techniques.

BACKGROUND AND OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is a method of life support for either isolated cardiac failure or respiratory failure, with or without cardiac failure. When used for hemodynamic support, the ECMO circuit presents a non-endothelialized, artificial surface to blood inciting an inflammatory response which activates haemostatic pathways. Anticoagulation may complicate a pre-existing coagulopathy and/or inadequate surgical hemostasis of varying severity. There is no standardized method to achieve and monitor anticoagulation or guide transfusion therapy during ECMO. We tested the hypothesis that institutions across the world conduct similar management of anticoagulation and transfusion during adult ECMO support. METHODS: This is a descriptive, self-reporting cross-sectional survey of anticoagulation and transfusion practice for patients age 18 or older on ECMO. This 38 multiple-choice question survey was sent to 166 institutions, internationally, utilizing adult ECMO. About 32·4% (54) of institutions responded. Responses were anonymously collected. Descriptive analyses were calculated. RESULTS: Our findings indicate there appears to be a significant practice variation among institutions regarding anticoagulation and transfusion during adult ECMO support. DISCUSSION: The lack of standard practices among institutions may reflect a paucity of data regarding optimal anticoagulation and transfusion for patients requiring ECMO. Standardized protocols for anticoagulation and transfusion may help increase quality of care for and reduce morbidity, mortality and cost to patients and healthcare centres. Further study is required for standardized, high quality care.

Effect of hypoxia on expression of selected proteins involved in regulation of apoptotic activity in striatum of newborn piglets.

The levels of selected neuroregulatory proteins that inhibit or promote apoptotic cell death were measured in the striatum of piglets subjected to precisely controlled 1 h hypoxic insult followed by 0, 2 and 4 h recovery and compared to sham operated animals. The anti-apoptotic proteins: there were increases in Survivin at 0 (157%, P = 0.031) and 4 h (171%, P = 0.033), in Bcl-XL at 0 (138%, P = 0.028) and 4 h (143%, P = 0.007), in VEGF at 4 h (185%, P = 0.019) and Hsp27 at 2 h (144%, P = 0.05) and 4 h (143%, P = 0.05). The pro-apoptotic proteins: caspases-1 and 7 increased at 4 h (135%, P = 0.05) and (129%, P = 0.038), respectively. Bim increased after 4 h (115%, P = 0.028), Apoptosis Inducing Factor after 2 h (127%, P = 0.048) and Calpain after 4 h (143% of control, P = 0.04). Hypoxia causes increase in levels of both anti- and pro-apoptotic proteins. Their relative activity determines the outcome in terms of cell damage and neuronal deficit.

Comparison of two ventilatory strategies in elderly patients undergoing major abdominal surgery.

BACKGROUND: 'Open lung' ventilation is commonly used in patients with acute lung injury and has been shown to improve intraoperative oxygenation in obese patients undergoing laparoscopic surgery. The feasibility of an 'open lung' ventilatory strategy in elderly patients under general anaesthesia has not previously been assessed. METHODS: 'Open lung' ventilation (recruitment manoeuvres, tidal volume 6 ml kg(-1) predicted body weight, and 12 cm H(2)O PEEP) (RM group) was compared with conventional ventilation (no recruitment manoeuvres, tidal volume 10 ml kg(-1) predicted body weight, and zero end-expiratory pressure) in elderly patients (>65 yr) undergoing major open abdominal surgery with regard to oxygenation, respiratory system mechanics, and haemodynamic stability. We also monitored the serum levels of the interleukins (IL)-6 and IL-8 before and after surgery to determine whether the systemic inflammatory response to surgery depends on the ventilatory strategy used. RESULTS: Twenty patients were included in each group. The RM group tolerated open lung ventilation without significant haemodynamic instability. Intraoperative Pa(o(2)) improved in the RM group (P<0.01) and deteriorated in controls (P=0.01), but postoperative Pa(o(2)) was similar in both groups. The RM group had improved breathing mechanics as evidenced by increased dynamic compliance (36%) and decreased airway resistance (21%). Both IL-6 and IL-8 significantly increased after surgery, but the magnitude of increase did not differ between the groups. CONCLUSIONS: A lung recruitment strategy in elderly patients is well tolerated and improves intraoperative oxygenation and lung mechanics during laparotomy.

Use of helium-oxygen mixtures to relieve upper airway obstruction in a pediatric population.

OBJECTIVES: Helium as a component of inspired gas decreases turbulent flow and airway resistance. Helium-oxygen mixtures have been used since the 1930s in the management of patients with upper airway obstruction. The objective of this study was to evaluate the efficacy of helium-oxygen mixtures in relieving upper airway obstruction in a pediatric population. STUDY DESIGN: Retrospective chart review of 42 pediatric patients who received helium-oxygen mixtures for upper airway obstruction within a 3-year period. METHODS: The study protocol included 42 pediatric patients, aged 1 week to 14 years, who were admitted to the Children's Hospital of Philadelphia from June 1997 to December 2000 and who received a total of 44 treatments of helium-oxygen therapy for upper airway obstruction. Response to treatment was determined by reduction in work of breathing noted on the chart. RESULTS: Thirty-two of 44 helium-oxygen treatments resulted in a positive response (73%). There were no significant differences in demographic characteristics between responders and nonresponders, except all of the premature infants were responders and 6 of the 9 patients with syndromes were nonresponders. CONCLUSIONS: Helium-oxygen therapy is a useful adjunct therapy for upper airway obstruction. Controlled clinical trials are necessary to better define the appropriate settings for use of helium-oxygen.

Improved early results with cavopulmonary connections.

BACKGROUND: We describe the recent results in a large cohort of patients with functionally single ventricle who underwent various modifications of cavopulmonary connections. METHODS: Using the database at our institution, we identified all children who underwent cavopulmonary connection operations between June 1995 and June 1997. Demographic data, surgical history, and perioperative course were reviewed. RESULTS: We performed 130 consecutive operations in 113 patients. The procedures included superior cavopulmonary connections in the form of the HemiFontan procedure in 45 instances, and bidirectional Glenn procedures in 11, and bilateral superior cavopulmonary connections in 7. The median age of these patients was 7.0 months. We completed Fontan operations using a fenestrated lateral tunnel on 47 occasions, and using an extracardiac conduit 9 times, 5 of which were fenestrated. A lateral tunnel without fenestration was constructed in one patient. The median age for these procedures was 19.5 months. In the remaining 10 instances, we revised Fontan procedures at a median age of 8 years. Diagnoses included hypoplastic left heart syndrome in 43 patients, double outlet right ventricle in 22, heterotaxy in 13, tricuspid atresia in 13, and a miscellaneous group accounting for the other 22. One death (0.7%) occurred within 30 days of surgery. Clinical seizures occurred in 7 children (5.3%), 6 had no residual neurologic deficits. Atrial pacing was needed in 14 children (10.7%) because of transient junctional rhythm, and 2 received treatment for supraventricular tachycardia. Pleural effusions were diagnosed radiographically after 31 of 130 (24%) procedures. Diuretic therapy resolved the effusion in 21 of these, with only 6 children requiring thoracostomy catheter drainage, and 4 undergoing thoracentesis alone. The median length of stay on the intensive care unit was 2 days, with a range from 1 to 30 days, and median stay in hospital was 6 days, with a range from 3 to 58 days. CONCLUSION: Mortality and perioperative morbidity after cavopulmonary connections have decreased dramatically in the current era. The long-term results of staged reconstruction for functionally single ventricle, nonetheless, await ongoing study.

Airway pressure release ventilation in pediatrics.

OBJECTIVES: The purpose of this study was to determine the effectiveness of airway pressure release ventilation in children. DESIGN: Prospective, randomized, crossover clinical trial. SETTING: This study was conducted in our 33-bed pediatric intensive care unit at The Children's Hospital of Philadelphia. PATIENTS: Patients requiring mechanical ventilatory support and weighing >8 kg were considered for enrollment. Patients were excluded if they required mechanical ventilatory support for >7 days or required >.50 Fio(2) for >7 days before enrollment. Patients with documented obstructive airway disease and congenital or acquired heart disease were excluded as well. INTERVENTIONS: Each patient received both volume-controlled synchronized intermittent mechanical ventilation (SIMV) and airway pressure release ventilation (APRV) via the Drager Evita ventilator (Drager, Lubeck, Germany). Measurements were obtained after the patient was stabilized on each ventilation mode. Stabilization was defined as oxygenation, ventilation, hemodynamic variables, and patient comfort within the acceptable range for each patient as determined by the bedside physician. After measurements were obtained on the initial mode of ventilation, the subjects crossed over to the alternative study mode. Stabilization was again achieved, and measurements were repeated. After completion of the second study measurements, patients were placed on the ventilation modality preferred by the bedside clinician and were followed through weaning and extubation. Measurements: Vital signs, airway pressures, minute ventilation, Spo(2), and E(T)CO(2) were recorded at enrollment and at each study condition. MAIN RESULTS: APRV provided similar ventilation, oxygenation, mean airway pressure, hemodynamics, and patient comfort as SIMV. Inspiratory airway pressures were lower with APRV when compared with SIMV. CONCLUSIONS: Using APRV in children with mild to moderate lung disease resulted in comparable levels of ventilation and oxygenation at significantly lower inspiratory peak and plateau pressures. Based on these findings, we plan to evaluate APRV in children with significant lung disease.

Cecal ligation and double puncture impairs heat shock protein 70 (HSP-70) expression in the lungs of rats.

Induction of the heat shock response may improve outcome from pathophysiological disturbances. This improvement is associated with and believed to result from expression of heat shock protein (HSP)-70. Therefore, we examined the temporal expression of HSP-70 in an animal model of acute respiratory distress syndrome (ARDS) secondary to fecal peritonitis. Specifically, we hypothesize that sepsis in rats impairs pulmonary HSP-70 expression. ARDS was induced in adolescent rats via cecal ligation and double puncture (2CLP). Sham-operated animals served as controls. Lung tissue was collected 0, 3, 6, 16, 24, and 48 h after 2CLP and sham operation. Northern blot hybridization analysis was performed to detect steady-state HSP-70 messenger ribonucleic (mRNA) levels. HSP-70 protein levels were determined via immunoblotting and immunohistochemistry. Mortality after 2CLP was 50% at 24 h and 75% at 48 h. Northern blot hybridization analysis revealed no significant change in steady-state HSP-70 mRNA levels in lung at any time after 2CLP. HSP-70 steady-state mRNA levels increased after sham operation and was higher than values in 2CLP at 6, 16, and 24 h. HSP-70 protein levels did not change over time in either group. Thus, the expression of HSP-70 does not change after 2CLP. Although lack of an increase in protein levels may be adaptive after sham operation, it is not appropriate after 2CLP. Therefore, failed HSP-70 expression represents a form of pulmonary epithelial dysfunction that may contribute to lung injury in sepsis.

Successful use of extracorporeal membrane oxygenation (ECMO) during BMT for SCID.

An 8-month-old girl with SCID presented with severe bronchiolitis. She received an HLA-identical sibling BMT without conditioning or GVHD prophylaxis. She deteriorated despite mechanical ventilation but had normal cardiac, hepatic and renal function. ECMO was instituted on day +3 and subsequent improvement was seen concurrently with emergence of CD4+ cells on day +11. She was taken off ECMO on day +18 and suffered a left-sided stroke evidenced by a dense left hemiplegia. She was extubated on day +25 and weaned from supplemental oxygen on day +36 and at day +100 has recovered strength in her extremities. This is the first successful use of ECMO as a bridge to engraftment in a BMT patient.

Chronic carbachol pretreatment decreases adenylyl cyclase activity in airway smooth muscle.

In airway smooth muscle, the regulation of adenylyl cyclase, the enzyme that synthesizes adenosine 3',5'-cyclic monophosphate, is under dual regulation by G protein-coupled receptors. It is unknown if chronic activation of muscarinic receptors in airway smooth muscle alters the stimulatory adenylyl cyclase cascade to decrease airway relaxation. Bovine airway smooth muscle pretreated with carbachol for 18 h, but not for 30 min or 2 h, showed decreased adenylyl cyclase activity under basal conditions and in response to isoproterenol, prostaglandin E1, GTP, and forskolin. The quantity of beta-adrenergic receptors or of Gi alpha proteins was unaffected by carbachol pretreatment. The effect of carbachol pretreatment was blocked by the inclusion of atropine or the protein kinase C (PKC) inhibitor staurosporine. These results suggest that chronic but not acute agonist pretreatment of muscarinic receptors decreases in adenylyl cyclase stimulation at a site distal to receptors and that this effect is mediated by the chronic activation of PKC via the M3 muscarinic receptor.

Common nutritional issues in pediatric and adult critical care medicine.

This article discusses many of the nutritional topics important to the intensivist. Nutritional assessment, substrate immunonutrition, and disease specific issues are presented. Early introduction of enteral feeds and the use of nutritional modulation are emphasized.

Oral water intoxication in infants. An American epidemic.

Between 1975 and 1990, a total of 34 patients with water intoxication were treated at St Louis (Mo) Children's Hospital, 24 of these in the last 3 years, indicating a marked increase in incidence of this previously rare condition. Thirty-one were infants living in poverty who ingested excessive amounts of water offered at home by their caretakers. Exhaustion of the supply of infant formula was the most common reason given for this substitution. Infants were treated by a single infusion of hypertonic saline or a slow infusion of isotonic saline. Central pontine myelinolysis was not observed as a complication of hypertonic saline therapy. Modification of the Special Supplemental Food Program for Women, Infants, and Children to provide sufficient formula for the growing infant and better education of mothers as to the hazards of excessive water ingestion might reduce the incidence of this preventable and life-threatening condition.

Modification of the sponge allograft model to study the immune response to bone marrow cells.

The sponge allograft model of Roberts & Hayry and of Ascher et al. was modified by introducing bone marrow cells into uncoated sponges 7 days after the sponge was implanted into the mouse. The number and cellular composition of the response in the sponges was essentially the same whether the stimulus was allogeneic or syngeneic bone marrow. However, the allogeneically stimulated sponge derived cells demonstrated allospecific cell-mediated lympholysis at very low effector-to-target ratios. Similar cytotoxic activity was difficult to demonstrate in splenic cells from the same animal tested concurrently. The cytotoxic cells were shown to be Lyt-1-, 2+ and Thy 1+. For a bone marrow impregnated sponge the peak T cell killing was reached after 12 days whereas peak killing occurred on day 14 in peritoneal cell infiltrated sponges as utilized by Ascher et al. Our model was developed to study the response to various antigenic stimuli placed into the sponge. This variation of the sponge allograft model should permit the study of a local cellular immune response to a number of antigens.