Arterial lactate for predicting mortality in children requiring extracorporeal membrane oxygenation.

BACKGROUND: Dynamic arterial lactate indices predict mortality more accurately than static arterial lactate measurements in children with septic shock or congenital cardiac defects. The current study evaluates whether this also applies to children with primary respiratory disease requiring extracorporeal membrane oxygenation (ECMO). METHODS: Static arterial lactate levels (LACabs) were prospectively collected before and during ECMO support for this single center, observational cohort study. Also, time-weighted arterial lactate (LACtw) and lactate change over time (LACdelta) were calculated as dynamic indices for, respectively, the duration and the trend over time of lactate derangement. Intensive care mortality was the primary endpoint. Analyses were performed for neonatal and pediatric patients separately. RESULTS: Fifty-six neonatal and 39 pediatric patients were included. Eighteen (32%) neonatal and 12 (31%) pediatric patients died. The evolution of LACabs and LACdelta differed between the pediatric survivors and the pediatric non-survivors (P<0.001, P=0.025). The hazard ratio was 1.23 (CI95=1.06-1.43, P=0.007) for LACabs and 20.64 (CI95=1.99-214.20, P=0.011) for LACdelta, indicating that higher lactate levels increase the risk for mortality. The predictive value for LACabs was 0.75 (CI95=0.57-0.93) and for LACdelta 0.69 (CI95=0.51-0.87), respectively. There were neither consistent differences for LACtw in the pediatric patients, nor for any of the static or dynamic lactate indices in the neonatal patients. CONCLUSION: Static arterial lactate measurements and, to a lesser extent, dynamic arterial lactate indices predict mortality in pediatric, but not neonatal ECMO patients. The magnitude and trend over time rather than the duration of lactate derangement are associated with mortality.

Challenges in non-neonatal extracorporeal membrane oxygenation.

This review will address the different challenges for the use of non-neonatal extracorporeal membrane oxygenation (ECMO). It will discuss the available evidence for the use of pediatric ECMO in respiratory and circulatory failure, focusing on indications and contra-indications and choice of ECMO mode. Furthermore we will try to define optimal treatment goals, identify primary outcome parameters and calculate the expected need for non-neonatal ECMO per 1.000.000 inhabitants.

Pharmacotherapy in neonatal and pediatric extracorporeal membrane oxygenation (ECMO).

ECMO support is an established life saving therapy for potentially reversible respiratory and/or cardiac failure. Improvement of outcome depends on effective treatment of the primary diagnosis and complications. Adequate drug therapy is important in reaching these goals. Pharmacokinetic and pharmacodynamic data in neonates and older children on ECMO are sparse. Most studies show altered volume of distribution and clearance for the drugs studied. This article gives an overview of the available PK and PD studies in neonates and children on ECMO, suggests possible mechanisms of altered PK and PD and identifies areas of interest for further research.

Evaluation of the antiviral response to zanamivir administered intravenously for treatment of critically ill patients with pandemic influenza A (H1N1) infection.

A retrospective nationwide study on the use of intravenous (IV) zanamivir in patients receiving intensive care who were pretreated with oseltamivir in the Netherlands was performed. In 6 of 13 patients with a sustained reduction of the viral load, the median time to start IV zanamivir was 9 days (range, 4-11 days) compared with 14 days (range, 6-21 days) in 7 patients without viral load reduction (P = .052). Viral load response did not influence mortality. We conclude that IV zanamivir as late add-on therapy has limited effectiveness. The effect of an immediate start with IV zanamivir monotherapy or in combination with other drugs need to be evaluated.

Feasibility of sedation and analgesia interruption following cannulation in neonates on extracorporeal membrane oxygenation.

PURPOSE: In most extracorporeal membrane oxygenation (ECMO) centers patients are heavily sedated to prevent accidental decannulation and bleeding complications. In ventilated adults not on ECMO, daily sedation interruption protocols improve short- and long-term outcome. This study aims to evaluate safety and feasibility of sedation interruption following cannulation in neonates on ECMO. METHODS: Prospective observational study in 20 neonates (0.17-5.8 days of age) admitted for ECMO treatment. Midazolam (n = 20) and morphine (n = 18) infusions were discontinued within 30 min after cannulation. Pain and sedation were regularly assessed using COMFORT-B and visual analog scale (VAS) scores. Midazolam and/or morphine were restarted and titrated according to protocolized treatment algorithms. RESULTS: Median (interquartile range, IQR) time without any sedatives was 10.3 h (5.0-24.1 h). Median interruption duration for midazolam was 16.5 h (6.6-29.6 h), and for morphine was 11.2 h (6.7-39.4 h). During this period no accidental extubations, decannulations or bleeding complications occurred. CONCLUSIONS: This is the first study to show that interruption of sedatives and analgesics following cannulation in neonates on ECMO is safe and feasible. Interruption times are 2-3 times longer than reported for adult ICU patients not on ECMO. Further trials are needed to substantiate these findings and evaluate short- and long-term outcomes.

Small-dose perfluorocarbon reduces the recruitment pressure needed to open surfactant-deficient atelectatic lungs.

BACKGROUND: This study was undertaken to investigate the effect of a small dose of perfluorocarbon on the recruitment pressure needed to open atelectatic lung areas. METHODS: In 12 Yorkshire pigs (body weight, 9 kg), lung injury was induced by whole lung lavage. After 1 h of conventional ventilation, an open lung maneuver was performed to obtain PaO2 values equal to the pre-lavage PaO2 values (+/-10%). After 1 h of ventilation at the lowest possible airway pressure that stabilized the recruited lung volume, the animals were disconnected from the ventilator to allow the lung to collapse. Six animals received a 5 ml/kg intratracheal dose of perfluorocarbon and a second open lung maneuver was performed. Six animals served as controls and received no perfluorocarbon but also underwent a second open lung maneuver. RESULTS: In both groups, an open lung maneuver resulted in a significant increase in oxygenation. The peak pressures needed to open the lung after 1 h of mechanical ventilation in the perfluorocarbon and control groups were 43.8 +/- 8.4 cmH2O and 46.6 +/- 4 cmH2O, respectively. The addition of perfluorocarbon significantly reduced the opening pressure to 34.5 +/- 6.3 cmH2O (P < 0.01), whereas the opening pressure in the control group, 45.0 +/- 0.2 cmH2O, did not change. CONCLUSION: The instillation of a small amount of perfluorocarbon significantly reduces the opening pressures needed to recruit atelectatic lung areas.

Propofol 6% as sedative in children under 2 years of age following major craniofacial surgery.

BACKGROUND: After alarming reports concerning deaths after sedation with propofol, infusion of this drug was contraindicated by the US Food and Drug Administration in children <18 yr receiving intensive care. We describe our experiences with propofol 6%, a new formula, during postoperative sedation in non-ventilated children following craniofacial surgery. METHODS: In a prospective cohort study, children admitted to the paediatric surgical intensive care unit following major craniofacial surgery were randomly allocated to sedation with propofol 6% or midazolam, if judged necessary on the basis of a COMFORT behaviour score. Exclusion criteria were respiratory infection, allergy for proteins, propofol or midazolam, hypertriglyceridaemia, familial hypercholesterolaemia or epilepsy. We assessed the safety of propofol 6% with triglycerides (TG) and creatine phosphokinase (CPK) levels, blood gases and physiological parameters. Efficacy was assessed using the COMFORT behaviour scale, Visual Analogue Scale and Bispectral Index monitor. RESULTS: Twenty-two children were treated with propofol 6%, 23 were treated with midazolam and 10 other children did not need sedation. The median age was 10 (IQR 3-17) months in all groups. Median duration of infusion was 11 (range 6-18) h for propofol 6% and 14 (range 5-17) h for midazolam. TG levels remained normal and no metabolic acidosis or adverse events were observed during propofol or midazolam infusion. Four patients had increased CPK levels. CONCLUSION: We did not encounter any problems using propofol 6% as a sedative in children with a median age of 10 (IQR 3-17) months, with dosages <4 mg kg(-1) h(-1) during a median period of 11 (range 6-18) h.

[Problematic care for a trauma patient with morbid obesity]. / Problematische traumazorg voor een patiënte met morbide obesitas.

A 33-year-old woman was trapped in a car following an accident. Because of her size (241 kg; BMI: 85 kg/m2) it was difficult to free, transport, examine and treat her. A few days after she had been discharged with a knee injury, she was again admitted for pneumonia. Partly as a result of para-infectious rhabdomyolysis, she died 5 days later. More and more people in The Netherlands are overweight, and more and more often to an extreme degree. Complicated accident kinetics, problems with diagnosis and treatment, comorbidity and an increased risk of complications in obese patients contribute to the poorer prognosis following blunt trauma. It is therefore practically impossible to give obese patients the usual care according to the protocol. Adaptations like positioning in the anti-Trendelenburg, left lateral-tilt position, as well as bigger and stronger equipment, may improve the care of trauma patients with morbid obesity.

Combining partial liquid ventilation with nitric oxide to improve gas exchange in acute lung injury.

OBJECTIVE: To assess the effects of increasing concentrations of inhaled nitric oxide (NO) during incremental dosages of partial liquid ventilation (PLV) on gas exchange, hemodynamics, and oxygen transport in pigs with induced acute lung injury (ALI). DESIGN: Prospective experimental study. SETTING: Experimental intensive care unit of a university. SUBJECTS: 6 pigs with induced ALI. INTERVENTIONS: Animals were surfactant-depleted by lung lavage to a partial pressure of oxygen in arterial blood (PaO2) < 100 mmHg. They then received four incremental doses of 5 ml/kg perflubron (Liqui-Vent). Between each dose the animals received 0, 10, 20, 30, 40, and 0 parts per million (ppm) NO. MEASUREMENTS AND MAIN RESULTS: Blood gases, hemodynamic parameters, and oxygen delivery were measured after each dose of perflubron as well as after each NO concentration. Perflubron resulted in a dose-dependent increase in PaO2. At each perflubron dose, additional NO inhalation resulted in a further significant (ANOVA, p < 0.05) increase in PaO2, with a maximum effect at 30 +/- 10 ppm NO. The 5 ml/kg perflubron dose led to a significant decrease in mean pulmonary artery pressure, which decreased further with higher NO concentrations. CONCLUSIONS: PLV can be combined with NO administration and results in a cumulative effect on arterial oxygenation and to a decrease in pulmonary artery pressure, without having any deleterious effect on measured systemic hemodynamic parameters.

Evaluation of lung function after intratracheal perfluorocarbon administration in healthy animals.

OBJECTIVES: To investigate the effects of partial liquid ventilation (i.e., mechanical ventilation in combination with intratracheal administration of perfluorocarbon) on lung function, with particular attention to the integrity of the alveolocapillary membrane in healthy adult animals. DESIGN: Prospective, randomized, controlled study. SETTING: Laboratory at the Department of Experimental Anesthesiology, Erasmus University Rotterdam. SUBJECTS: Ten adult male New Zealand rabbits. INTERVENTIONS: Five rabbits were intratracheally treated with 12 mL/kg of perfluorocarbon while conventional mechanical ventilation (volume-controlled, tidal volume of 12 mL/kg, respiratory rate of 30 breaths/min, inspiration/expiration ratio of 1:2, positive end-expiratory pressure of 2 cm H2O, and an FIO2 of 1.0) was applied for 3 hrs. To assess the permeability of the alveolocapillary membrane, pulmonary clearance of inhaled technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) measurements were performed at 3 hrs and compared with data from the control group (n = 5) treated with mechanical ventilation only, using the same ventilatory parameters. MEASUREMENTS AND MAIN RESULTS: Pulmonary gas exchange and lung mechanical parameters were measured in both groups at 30-min intervals. Mean values for PaO2 in the perfluorocarbon group, although at adequate levels, were less than those values of the control group during the 3-hr study period (370 +/- 44 vs. 503 +/- 44 torr at 3 hrs [49.3 +/- 5.9 vs. 67.1 +/- 5.9 kPa]). Peak and mean airway pressures were higher in the perfluorocarbon group (ranging from 1.9 to 3.4 cm H2O and 0.7 to 1.3 cm H2O, respectively) compared with the control group, while end-inspiratory airway pressure was similar in both groups. The half-life of 99mTc-DTPA was 83.7 +/- 24.5 mins in the control group, which was significantly longer (p < .01) than in the perfluorocarbon group (49.8 +/- 6.1 mins). CONCLUSIONS: These findings suggest that partial liquid ventilation with perfluorocarbons lowers pulmonary gas exchange in healthy animals, and the increased pulmonary clearance of 99mTc-DTPA after 3 hrs of this type of ventilatory support may reflect minimal reversible changes in the lung surfactant system.

Hemodynamic effects of partial liquid ventilation with perfluorocarbon in acute lung injury.

OBJECTIVE: To assess the effect of partial liquid ventilation with perfluorocarbons on hemodynamics and gas exchange in large pigs with induced acute lung injury (ALI). DESIGN: Randomized, prospective, double-control, experimental study. Experimental intensive care unit of a university. MATERIALS: Eighteen large pigs (50 +/- 5 kg body weight) with an average anterior posterior thoracic diameter of 24 cm and induced acute lung injury. INTERVENTIONS: All animals were surfactant depleted by lung lavage to a PaO2 below 100 mmHg and randomized to receive either perflubron (n = 6) or saline (n = 6) in five intratracheal doses of 5 ml/kg at 20-min intervals, or no instillation (n = 6). MEASUREMENTS AND RESULTS: In all animals heart rate, arterial pressures, pulmonary pressures, cardiac output and blood gases were recorded at 20-min intervals. There was no deleterious effect on any hemodynamic parameter in the perflubron group, whereas systolic and mean pulmonary arterial pressure values showed a persistent decrease after the first 5 ml/kg of perflubron, from 48.7 +/- 14.1 to 40.8 +/- 11.7 mmHg and from 39.7 +/- 13.2 to 35.2 +/- 12.0 mmHg, respectively. Perflubron resulted in a significant (ANOVA P < 0.01), dose-dependent increase in PaO2 values from 86.3 +/- 22.4 to a maximum of 342.4 +/- 59.4 mmHg at a dose of 25 ml/kg; the other groups showed no significant increase in PaO2. CONCLUSIONS: Tracheal instillation of perflubron in induced ALI results in a dose-dependent increase in PaO2 and has no deleterious effect on hemodynamic parameters.

Comparison of ketorolac and morphine for postoperative pain after major surgery.

This study was designed to determine the relative analgesic efficacy and safety of single intramuscular injections of ketorolac (10 mg or 30 mg) and morphine (10 mg) in patients of either sex with moderate to severe pain after major surgery. In a single-dose, randomised, double-blind study of parallel design, pain was assessed immediately before injection of test medication and at regular intervals for 8 h thereafter. One hundred and seventeen patients (109 undergoing cardiac surgery; 8 lung surgery) were randomized to one of the three treatment groups. Pain intensity was assessed using a 5-point verbal scale before administration of study drugs. Postadministration, at 30 min and hourly for 8 h, pain intensity and pain relief were assessed, again using the 5-point verbal scale. Additionally, as a measure of analgesia, forced expiratory volume (FEV1) was obtained in all patients. Vital signs including blood pressure, pulse, temperature, respiratory rate and blood gases (PaCO2) were recorded prior to and after study medication. Based on hourly pain intensity differences and hourly pain relief observations, ketorolac 10 mg was generally more effective than morphine 10 mg, and ketorolac 30 mg was generally more effective than ketorolac 10 mg. The results of this study show that ketorolac is an effective and safe (with regard to arterial pressure, blood gases and lung function) analgesic for relief of postoperative pain after major surgery in stable patients. No clinically significant adverse effects occurred during the study. One cannot exclude an influence on patients with organ system dysfunction or on parameters not measured in this study.

Efficacy and safety of tramadol versus morphine for moderate and severe postoperative pain with special regard to respiratory depression.

The analgesic efficacy and safety of tramadol and morphine were compared in a double-blind, randomized study of 150 female patients after gynecologic surgery. As required, patients could receive up to three intravenous doses of either 50 mg of tramadol or 5 mg of morphine within a period of 6 h. Pain intensity (verbal response score) was recorded before injection and at 0.5, 1, 2, 3, 5, and 6 h after the initial dose; at these times, pain relief was also assessed. Oxygen saturation was monitored continuously by pulse oximetry for at least 30 min after each injection. In 13.3% of the morphine group (but in none of the tramadol group) transcutaneous pulse oxygen saturation decreased to less than 86%; in 50% of these patients the decrease occurred after only the first 5 mg of morphine. Both drugs produced acceptable analgesia, and there were no clinically significant adverse events. In demonstrating the absence of clinically relevant respiratory depression with tramadol, we underline its safety for postoperative pain relief.