Haemodynamic changes and stress responses of piglets to surgery during total intravenous anaesthesia with propofol and fentanyl.

The purpose of the study was to assess the haemodynamic (blood pressure and heart rate) changes and stress responses (serum cortisol and serum amyloid A [SAA] concentrations) to surgery in piglets during total intravenous anaesthesia (TIVA) with propofol and fentanyl. After preanaesthetic medication with intramuscular midazolam (0.5 mg/kg body mass), ketamine (10 mg/kg) and butorphanol (0.5 mg/kg) anaesthesia was induced in five piglets, with intravenous propofol (1 mg/kg) followed by tracheal intubation and mechanical lung ventilation. Soft tissue surgery was performed in the jugular and inguinal regions during TIVA with propofol (8 mg/kg/h) and fentanyl (35 microg/kg/h). Anaesthesia was maintained for 300 min after surgery as the piglets were the control group of a project involving extracorporeal membrane oxygenation. Mean plasma cortisol concentration decreased significantly (P<0.05) from 59+/-39.9 nmol/L (mean+/-1 SD) before surgery to 7.5+/-2.5 nmol/L 300 min after end of surgical procedure. The mean SAA concentrations increased over the same period from 1.6+/-2.3 microg/mL to 4.2+/-5.6 microg/mL without statistical significance. The baseline (presurgery) mean arterial pressure (MAP) was 72+/-9 mmHg compared with 72+/-11 mmHg 300 min after end of surgery. Neither heart rate nor lactate concentrations changed significantly over the same time points: heart rate was 104+/-11 and 103+/-15 beats/min whereas mean lactate concentrations were reduced from 1.14+/-0.45 mmol/L to 0.90+/-0.22 mmol/L. Haemodynamic stability, a decrease in serum cortisol and a non-statistically significant rise in mean SAA concentrations suggest that the anaesthetic described suppresses the stress response of piglets to surgery without adverse cardiovascular effects. Therefore, it may prove useful in cardiovascular research.

The immediate haemodynamic response to the initiation of extracorporeal membrane oxygenation in a piglet model of infant hypoxic respiratory failure.

There is evidence that haemodynamic fluctuations on extracorporeal membrane oxygenation (ECMO) increase the risk of cerebral damage. We hypothesized that initiation of venovenous (VV) or venoarterial (VA) ECMO itself causes haemodynamic fluctuations and, thus, established an infant animal ECMO model in order to discuss this hypothesis. Five piglets were cannulated using the jugular and femoral veins (VV group) and five using the jugular vein and carotid artery (VA group). All animals were subjected to hypoxic ventilation (FiO2 8%) for 10 min, leading to a PaO2 of < 40 mmHg, and subsequently rescued by ECMO. The heart rate (HR) and mean arterial blood pressure (MAP) were recorded at 5-min intervals; the arterial blood lactate was measured prior to and after 5 and 10 min of hypoxia, as well as 30, 60 and 120 min after initiation of ECMO. The response to initiation of ECMO was similar in the VV and VA groups with regard to HR and lactate, but differed significantly in MAP. HR decreased significantly from 135 +/- 7 to 103 +/- 6 beats/min (p < 0.05) and from 132 +/- 8 to 84 +/- 9 beats/min (p < 0.01) at 5 min (p = NS) after installation; lactate increased from 1.4 +/- 0.1 to 1.8 +/- 0.2 mmol/l (p = NS) and from 1.4 +/- 0.2 to 1.6 +/- 0.5 mmol/l (p = NS) after 30 min (p = NS); MAP decreased from 80 +/- 5 to 63 +/- 3 mmHg (p = NS) and increased from 75 +/- 4 to 84 +/- 3 mmHg (p = NS) at 5 min (p = 0.001), respectively. The initiation of ECMO is associated with haemodynamic fluctuations in both modalities, which differ with regard to blood pressure reaction.

Osteomyelitis at the injection site of adrenalin through an intraosseous needle in a 3-month-old infant.

Intraosseous (IO) puncture is considered for the administration of drugs and fluids when vascular access cannot be achieved rapidly. Adrenaline/epinephrine, adenosine, crystalloids, colloids and blood products can be applied and administered effectively using this route during resuscitation of children. This technique is relatively simple with complications of <1%. These may include tibial fracture, lower extremity compartment syndrome and osteomyelitis. A case is described in which a 3-month-old male infant presented for emergency resuscitation requiring IO infusion utilising both tibial bones. High doses of adrenaline (1:1000; 0.1 mg/kg) were administered in the right tibial epiphysis only after the standard initial concentration (1:10000; 0.01 mg/kg) had minimal effect. A local inflammatory reaction was noted 24 h later in the right tibial region, which developed into cutaneous necrosis, and was eventually resected. Radiologically, no osseous lesion could be demonstrated, however, a bone scintigram revealed osteomyelitis. Upon surgical revision, purulent destruction was evident requiring removal of the epiphysis and part of the metaphysis. Although osteomyelitis is a rare complication which may be caused by sepsis, or contamination during insertion, we speculate that adrenaline in high concentrations may promote the development of osteomyelitis and the drug should be applied cautiously in more diluted concentrations.

Life threatening cardiopulmonary failure in an infant following protamine reversal of heparin after cardiopulmonary bypass.

Life threatening cardiopulmonary failure following protamine reversal of heparin after cardiopulmonary bypass (CPB) was reported to occur in adults but rarely in children. Atrial septal defect closure was performed in a 6-week-old infant erroneously suspected to suffer from right atrial thrombosis in addition. Protamine administration after CPB led to critical pulmonary hypertension and severe haemorrhagic pulmonary oedema resulting in severe hypoxia. Inhaled nitric oxide, together with high frequency oscillation ventilation supplemented by intravenous prostacycline, enabled complete recovery of cardiopulmonary and neurological function. Life threatening cardiovascular compromise after intravenous protamine can occur even in young infants which then require challenging paediatric critical care.

Severe respiratory failure following charcoal application in a toddler.

Charcoal has been commonly used for enteral detoxication with few adverse effects. In toddlers charcoal can often be simply applied via a gastric tube. Regurgitation and aspiration is considered a rare event. We report the case of a 19-month-old boy who suffered endobronchial charcoal contamination followed by acute airway obstruction and severe respiratory failure despite a commonly used tube placement verification technique. Immediate intubation, tracheal suctioning, intravenous bronchodilators, and high frequency oscillatory ventilation (HFOV) were used to control hypercarbia and hypoxia. Eventually charcoal removal by bronchoscopy was successful. Chest X-ray investigation did not reflect the true amount of charcoal deposited endobronchially at any time. We conclude that gastric tube application of charcoal in children carries a risk of aspiration. This may lead to life-threatening respiratory failure with the need to provide artificial ventilation and bronchial lavage.

A pulsatile pneumatically driven neonatal extracorporeal membrane oxygenation system using neck vessel cannulas tested with neonatal mock circulation.

In posthypoxic circulatory failure, pulsatility of flow generated by mechanical support devices significantly influences outcome. Pneumatically driven assist devices can create highly pulsatile flow, but need large graft cannulas implanted by thoracotomy in children and neonates. Emergency application is therefore hindered. We conducted an in vitro study using neonatal mock circulation (NMC) to test whether an extracorporeal membrane oxygenation (ECMO) system driven by a commercially available pneumatic assist device also can be operated through commonly used neonatal neck vessel cannulas. Using the pneumatically operated Medos ventricular assist device (VAD) 10 ml ventricle along with the Jostra M8/HEC40 oxygenator/heat exchanger, a neonatal ECMO system was assembled and connected to the NMC by means of commercially available neonatal neck vessel cannulas. Effective ECMO flow, combined circulation flow, and circulation pressures were measured during various working settings (ventricle driving pressures [systolic/diastolic (mbar)]: low: +100/-25, moderate: +200/-50, high: +300/-99) and loading conditions (device working against 0, 50, and 100% native circulation flow). Additionally, maximum possible ECMO flow through various sizes of neonatal ECMO cannulas and resulting pressure gradients were assessed. High pressure settings were necessary to achieve 100 ml/kg/min pulsatile circulation flow in case of zero native circulation. With residual 30% native circulation flow, 100 ml/kg/min pulsatile circulation flow could be established by moderate pressure settings. Low preload or high systemic vascular resistance reduced ECMO flow markedly. We concluded that in the described setting a pneumatically driven neonatal ECMO system could be operated even through commonly used neonatal neck vessel cannulas. It was necessary to accept partial emptying of the artificial ventricle and tapering of driving pressures with increasing native circulation.

Neonatal and pediatric extracorporeal membrane oxygenation using nonocclusive blood pumps: the Vienna experience.

Neonatal and pediatric extracorporeal membrane oxygenation (ECMO) is carried out commonly using occlusive blood pumps. Centrifugal pumps provide simple and safe technology for transportation on ECMO. The assistence respiratoire extra corporelle (AREC) system enables single needle venovenous ECMO for infants. We report on our experience with neonatal and pediatric ECMO treatments using nonocclusive blood pumps. One-hundred forty-six ECMO treatments were performed for cardiac, neonatal, and pediatric indications in 54, 19, and 27% of cases. Centrifugal pumps were used in 99, and the AREC system in 42 cases. Hospital mortality was estimated retrospectively and influence of type of pump, type of ECMO belonging to indication group, and lactate at ECMO installation were estimated. Irreversible organ failure leading to ECMO termination was investigated within groups of indications. Survival (recent 50 ECMO treatments) was 80, 70, 43, and 30% after meconium aspiration syndrome, acute respiratory distress syndrome, cardiac surgery, and prolonged resuscitation. Lactate exceeding 100 mg/dl at ECMO installation predicted significantly worse outcome. Cerebral damage was the main reason for ECMO termination in all but persistent circulatory failure in the cardiac group. Myocardial recovery resulted in all except 2 cardiac cases. Nonocclusive blood pumps can be used safely in neonatal and pediatric ECMO. Early installation may improve outcome markedly. In cardiac cases results of surgery should be thoroughly investigated on the table before ECMO installation to prevent hopeless ECMO treatments.

Permissive hypoxemia permitted postoperative weaning from artificial ventilation after repair of pulmonary atresia.

Survival after corrective surgery of pulmonary atresia was associated with low right ventricular pressure, indicating normal pulmonary vascular resistance. Therefore increased fractional inspiratory oxygen concentration, inhaled nitric oxide and intravenous prostacyclin were considered to be effective measures during postoperative intensive care. In a 20-year-old female, conduit repair and unifocalisation of pulmonary atresia with ventricular septal defect and systemic to pulmonary arterial collaterals were performed despite preexisting one-sided pulmonary hypertension. During the following postoperative period, normal arterial oxygen saturation aimed at by means of a high fractional inspiratory oxygen concentration, resulted in persistent pulmonary oedema despite fluid restriction. After several trials of weaning from artificial ventilation, permissive hypoxemia was eventually successful.

Intravenous prostacyclin mitigates inhaled nitric oxide rebound effect: A case control study.

Although extracorporeal membrane oxygenation (ECMO) improves oxygenation, pulmonary vascular resistance may be increased due to endothelial function impairment. Inhaled nitric oxide (iNO) is increasingly used for treatment of pulmonary hypertension after surgical repair of congenital heart defects, with or without ECMO. One of the main complications of its application is deterioration of oxygenation following withdrawal of iNO. To test whether intravenous prostacyclin applied prior to and during iNO withdrawal can mitigate this rebound effect, we conducted a retrospective case control study. The rebound effect was defined as a 5% decrease of oxygenation saturation within 4 h after iNO withdrawal. Twelve children suffering from pulmonary hypertension (2 after ECMO) and treated with iNO received 10 ng/kg/min prostacyclin intravenously 24 h prior to iNO withdrawal (Group 1). Twelve children treated with iNO (3 after ECMO) who received no prostacyclin prior to iNO withdrawal were matched as controls. The rebound effect occurred in 1 out of 12 children in Group 1 and in 8 out of 12 children in Group 2 (p = 0. 0039). We conclude that application of intravenous prostacyclin prior to and during iNO withdrawal may be able to mitigate the rebound effect.

Proposed entry criteria for postoperative cardiac extracorporeal membrane oxygenation after pediatric open heart surgery.

While extracorporeal membrane oxygenation (ECMO) is being used increasingly after pediatric cardiac surgery, criteria are lacking for initiating ECMO after bypass weaning. To develop clinically useful ECMO entry criteria based on parameters readily available, children were examined at postoperative pediatric intensive care unit (PICU) admission. Using hospital mortality as the primary outcome, univariate and multiple logistic regressions were performed to estimate the predictive value of clinical (age, weight, and diagnosis) and laboratory (arterial blood pressure, pH, lactate, creatine kinase, and arterial and central venous oxygen saturation [ScvO2]) variables. Data from 218 children over a 2 year period were analyzed retrospectively. Univariate regression demonstrated that age, weight, diagnosis, blood pressure, venous and arterial saturation, and lactate were significantly associated with postoperative mortality (p < 0.05). In multiple regression, ScvO2 and lactate level were found to be independent predictors and were used in a predictive model (ScvO2 odds ratio: 2.03-828.6, p = 0.016) (lactate odds ratio: 1.58 -4.20, p = 0.0002) (R2 = 0.70). Applying an 80% risk of mortality to establish entry criteria as in neonatal ECMO, PICU admission values of lactate > 70 mg/dl if ScvO2 < 60% or lactate >163 mg/dl if ScvO2 > 60% are proposed to serve as postoperative ECMO entry criteria if bypass weaning has been possible but is followed by low cardiac output.

Issues of pharmacology in pediatric cardiac extracorporeal membrane oxygenation with special reference to analgesia and sedation.

Sufficient analgesia, sedation, and paralysis, if necessary, are cornerstones of extracorporeal membrane oxygenation (ECMO) treatment protocols. However, increased distribution volumes, drug absorption by circuit materials, and impaired drug elimination, as well as alternations of cerebral perfusion and blood brain barrier function, result in the markedly altered pharmacodynamics of applied drugs. Today, narcotics combined with benzodiazepines, sometimes enforced by barbiturates, are commonly used in clinical practice. Paralysis is usually achieved by pancuronium or vecuronium. Although these drugs are used widely, actual efficacy remains uncertain because of the lack of reliable tools to measure pain relief and degree of sedation during ECMO, especially during paralysis. Taking into account the detrimental effects of insufficient pain relief and inadequate sedation in such unstable patients as children during pediatric cardiac ECMO, further studies on this topic seem urgently necessary.

Early detection of neurologic injury and issues of rehabilitation after pediatric cardiac extracorporeal membrane oxygenation.

Neurological impairment results in a significant population of children after extracorporeal membrane oxygenation (ECMO) for treatment of otherwise intractable circulatory failure. Pre-ECMO hypoxia/ischemia, reperfusion injury, and impaired cerebral perfusion during low output situations possibly aggravated by harmful effects of a pulsatile perfusion are discussed in terms of possible etiological reasons. To develop preventive strategies or to enable curative measure, early detection of neuronal injury seems mandatory. Electroencephalographic surveillance and/or monitoring of evoked potentials and monitoring of cerebral oxygenation by means of near infrared spectroscopy or jugular venous bulb oxygen saturation, as well as measurements of serum neuron specific enolase, S-100 protein, and brain type creatine kinase can be employed clinically. To improve functional outcome following neuronal injury, early rehabilitation seems essential to minimize the resulting effects on physical, cognitive, and emotional development.

Pulmonary failure after Norwood procedure: indication for extracorporeal membrane oxygenation? A case report.

Today some authors consider univentricular repair a contraindication for postoperative cardiac extracorporeal membrane oxygenation (ECMO). The question is whether or not ECMO is indicated as pulmonary support in case of an overwhelming pulmonary infection during the postoperative course after a Norwood procedure. During the prolonged weaning period after a Norwood procedure using a 4 mm aortopulmonary shunt, proven respiratory syncytial virus (RSV) bronchiolitis occurred at the time of expected weaning from artificial ventilation. Venovenous ECMO was able to improve oxygenation, but when pulmonary opacification failed to resolve, ECMO was terminated after 12 days.

Aortopulmonary collateral artery embolization during postoperative extracorporeal membrane oxygenation after arterial switch procedure.

Aortopulmonary collateral arteries sometimes complicate cyanotic congenital heart defects. Combined with a relevant left-right shunt, this could result in massive airway bleeding during and after corrective surgery. A preoperatively diagnosed 1.2 mm small aortopulmonary collateral artery in a newborn suffering from transposition of the great arteries caused life-threatening airway bleeding during surgery. Postoperative extracorporeal membrane oxygenation (ECMO) was necessary, and coil embolization was performed on ECMO to terminate pulmonary bleeding.

Extracorporeal membrane oxygenation discontinuation despite technically successful reoperation: A case report.

Death remains a probable outcome of pediatric cardiac extracorporeal membrane oxygenation (ECMO) despite increasing efforts to improve the results. On venoarterial ECMO, in an obviously hopeless situation, the decision to withdraw a life supporting measure resulting in the sudden death of a child places a heavy burden on the team. After valvulotomy of critical aortic stenosis in a prenatally diagnosed term neonate, ECMO had to be installed during postoperative resuscitation. Despite technically successful homograft implantation while on ECMO complicated by postoperative bleeding, advancing multiorgan failure resulted in ECMO withdrawal. As shown in this case report, exact termination criteria are lacking but are necessary to prevent increasing team and resource related conflicts in pediatric cardiac ECMO.

A centrifugal pump driven tidal flow extracorporeal membrane oxygenation system tested with neonatal mock circulation.

In 1993, Chevalier published his experiences with tidal flow venovenous extracorporeal membrane oxygenation (ECMO) featuring a single lumen cannula, non-occlusive roller pump, and alternating clamps. Using a neonatal mock circulation (NMC), which enables different hemodynamic states for neonatal ECMO research, the tested hypothesis was that it is possible to create a centrifugal pump driven tidal flow neonatal venovenous ECMO system. Additionally, the resulting hemodynamic effects in a condition of circulatory impairment were investigated. The ECMO circuit tested was assembled using a pediatric centrifugal pump head, a distensible reservoir, and a rotary clamp separating drainage from the injection phase. Using the NMC, end tidal volumes, mock circulation flow, and arterial and venous pressures were measured at different pump speeds after the drainage and injection phases. Effective venovenous ECMO flow (evvEF) was calculated. Mock circulation baseline values (ECMO clamped) were compared to values during tidal flow ECMO. At 3,000 rpm, a centrifugal pump speed of 75 ml/kg/min evvEF was reached, and it increased with higher pump speeds. At this point, the end tidal mock circulation flow (representing cardiac output) after drainage differed significantly from that during the injection phase (p < 0.01) but not from the baseline value. The end tidal arterial and venous pressures after the drainage phase were found to be significantly decreased compared to the baselines (p < 0.01). In conclusion, a centrifugal pump driven tidal flow venovenous ECMO system can be created enabling sufficient tidal volumes. Tested in the described NMC simulating posthypoxic circulatory impairment, significant hemodynamic effects could be demonstrated. Animal experiments for confirmation are necessary.