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Moronke A Noah,
Giles J Peek,
Simon J Finney,
Mark J Griffiths,
David A Harrison,
Richard Grieve,
M Zia Sadique,
Jasjeet S Sekhon,
Daniel F McAuley, Richard K Firmin, [......],
Susanna Price,
Alain Vuylsteke,
David P Jenkins,
David W Noble,
Roxanna Bloomfield,
Timothy S Walsh,
Gavin D Perkins,
David Menon,
Bruce L Taylor,
Kathryn M Rowan
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ABSTRACT: Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients with severe acute respiratory distress syndrome (ARDS), but its role has remained controversial. ECMO was used to treat patients with ARDS during the 2009 influenza A(H1N1) pandemic.
To compare the hospital mortality of patients with H1N1-related ARDS referred, accepted, and transferred for ECMO with matched patients who were not referred for ECMO.
A cohort study in which ECMO-referred patients were defined as all patients with H1N1-related ARDS who were referred, accepted, and transferred to 1 of the 4 adult ECMO centers in the United Kingdom during the H1N1 pandemic in winter 2009-2010. The ECMO-referred patients and the non-ECMO-referred patients were matched using data from a concurrent, longitudinal cohort study (Swine Flu Triage study) of critically ill patients with suspected or confirmed H1N1. Detailed demographic, physiological, and comorbidity data were used in 3 different matching techniques (individual matching, propensity score matching, and GenMatch matching).
Survival to hospital discharge analyzed according to the intention-to-treat principle.
Of 80 ECMO-referred patients, 69 received ECMO (86.3%) and 22 died (27.5%) prior to discharge from the hospital. From a pool of 1756 patients, there were 59 matched pairs of ECMO-referred patients and non-ECMO-referred patients identified using individual matching, 75 matched pairs identified using propensity score matching, and 75 matched pairs identified using GenMatch matching. The hospital mortality rate was 23.7% for ECMO-referred patients vs 52.5% for non-ECMO-referred patients (relative risk [RR], 0.45 [95% CI, 0.26-0.79]; P = .006) when individual matching was used; 24.0% vs 46.7%, respectively (RR, 0.51 [95% CI, 0.31-0.81]; P = .008) when propensity score matching was used; and 24.0% vs 50.7%, respectively (RR, 0.47 [95% CI, 0.31-0.72]; P = .001) when GenMatch matching was used. The results were robust to sensitivity analyses, including amending the inclusion criteria and restricting the location where the non-ECMO-referred patients were treated.
For patients with H1N1-related ARDS, referral and transfer to an ECMO center was associated with lower hospital mortality compared with matched non-ECMO-referred patients.
JAMA The Journal of the American Medical Association 10/2011; 306(15):1659-68. · 30.03 Impact Factor
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Moronke A Noah,
Michael Dawrant,
Gail M Faulkner,
Anne-Marie Hill,
Chris Harvey,
Abid Hussain,
David R Jenkins,
Sanjiv Nichani,
Giles J Peek,
Andrew W Sosnowski, Richard K Firmin
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ABSTRACT: Panton-Valentine leukocidin expressing Staphylococcus aureus pneumonia, an infection that affects predominantly young people, has a mortality rate of > 70% despite aggressive conventional management. Little information is available on the management of patients with Panton-Valentine leukocidin expressing S. aureus pneumonia with extracorporeal membrane oxygenation support. As a large extracorporeal membrane oxygenation center, we reviewed our experience and outcomes with Panton-Valentine Leukocidin expressing S. aureus pneumonia.
Locally held register of all extracorporeal membrane oxygenation patients at Glenfield Hospital.
Retrospective study including all patients with sputum-positive Panton-Valentine leukocidin expressing S. aureus pneumonia managed with extracorporeal membrane oxygenation support at a single extracorporeal membrane oxygenation center.
On review of our database held from September 1989 until date, there were four patients with sputum-confirmed Panton-Valentine leukocidin expressing S. aureus pneumonia managed with extracorporeal membrane oxygenation. Refractory hypoxemia and/or uncompensated hypercapnia despite optimal conventional management were the indications for extracorporeal membrane oxygenation. After varying periods on extracorporeal membrane oxygenation with appropriate antibiotic and ancillary care, all four patients were discharged home.
Panton-Valentine leukocidin expressing S. aureus pneumonia can cause severe, necrotizing pneumonia associated with acute respiratory distress syndrome, which can be particularly challenging to manage. Extracorporeal membrane oxygenation support permits low pressure lung ventilation, avoiding barotrauma to lungs made friable by Panton-Valentine leukocidin expressing S. aureus infection. Although this is a small number of patients, the results are encouraging.
Critical care medicine 11/2010; 38(11):2250-3. · 6.37 Impact Factor
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ABSTRACT: Congenital diaphragmatic hernia and oculocutaneous albinism are both rare birth defects that can be diagnosed in the newborn period. However, they have not been previously reported to have occurred together. This report describes a unique case of a male Asian baby with oculocutaneous albinism and a right-sided congenital diaphragmatic hernia.
Journal of Pediatric Surgery 12/2009; 44(12):e21-2. · 1.45 Impact Factor
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ABSTRACT: Recurrent wheezing in children is frequently due to asthma and responds to bronchodilator therapy. We report a case of a 13-year old boy with a 2-year history of presumed asthma not responding to bronchodilator therapy. Bronchoscopy revealed a right main bronchus tumor, which was diagnosed as bronchial schwannoma after resection by sleeve lobectomy. We review the literature on this tumor.
Journal of Asthma 10/2009; 46(8):856-7. · 1.52 Impact Factor
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Giles J Peek,
Miranda Mugford,
Ravindranath Tiruvoipati,
Andrew Wilson,
Elizabeth Allen,
Mariamma M Thalanany,
Clare L Hibbert,
Ann Truesdale,
Felicity Clemens,
Nicola Cooper, Richard K Firmin,
Diana Elbourne
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ABSTRACT: Severe acute respiratory failure in adults causes high mortality despite improvements in ventilation techniques and other treatments (eg, steroids, prone positioning, bronchoscopy, and inhaled nitric oxide). We aimed to delineate the safety, clinical efficacy, and cost-effectiveness of extracorporeal membrane oxygenation (ECMO) compared with conventional ventilation support.
In this UK-based multicentre trial, we used an independent central randomisation service to randomly assign 180 adults in a 1:1 ratio to receive continued conventional management or referral to consideration for treatment by ECMO. Eligible patients were aged 18-65 years and had severe (Murray score >3.0 or pH <7.20) but potentially reversible respiratory failure. Exclusion criteria were: high pressure (>30 cm H(2)O of peak inspiratory pressure) or high FiO(2) (>0.8) ventilation for more than 7 days; intracranial bleeding; any other contraindication to limited heparinisation; or any contraindication to continuation of active treatment. The primary outcome was death or severe disability at 6 months after randomisation or before discharge from hospital. Primary analysis was by intention to treat. Only researchers who did the 6-month follow-up were masked to treatment assignment. Data about resource use and economic outcomes (quality-adjusted life-years) were collected. Studies of the key cost generating events were undertaken, and we did analyses of cost-utility at 6 months after randomisation and modelled lifetime cost-utility. This study is registered, number ISRCTN47279827.
766 patients were screened; 180 were enrolled and randomly allocated to consideration for treatment by ECMO (n=90 patients) or to receive conventional management (n=90). 68 (75%) patients actually received ECMO; 63% (57/90) of patients allocated to consideration for treatment by ECMO survived to 6 months without disability compared with 47% (41/87) of those allocated to conventional management (relative risk 0.69; 95% CI 0.05-0.97, p=0.03). Referral to consideration for treatment by ECMO led to a gain of 0.03 quality-adjusted life-years (QALYs) at 6-month follow-up [corrected]. A lifetime model predicted the cost per QALY of ECMO to be pound19 252 (95% CI 7622-59 200) at a discount rate of 3.5%.
We recommend transferring of adult patients with severe but potentially reversible respiratory failure, whose Murray score exceeds 3.0 or who have a pH of less than 7.20 on optimum conventional management, to a centre with an ECMO-based management protocol to significantly improve survival without severe disability. This strategy is also likely to be cost effective in settings with similar services to those in the UK.
UK NHS Health Technology Assessment, English National Specialist Commissioning Advisory Group, Scottish Department of Health, and Welsh Department of Health.
The Lancet 09/2009; 374(9698):1351-63. · 38.28 Impact Factor
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ABSTRACT: Extracorporeal membrane oxygenation has been shown to be effective in term neonates with severe but reversible lung disease within the context of randomized, controlled trials. Extracorporeal membrane oxygenation now has been open to a wider population of infants in the United Kingdom, and other treatments have become available. The population referred for extracorporeal membrane oxygenation, therefore, has changed. The aims of this study were to (1) compare respiratory outcomes of infants who received extracorporeal membrane oxygenation in recent years with those from 10 years ago and (2) determine whether respiratory outcome varied with diagnostic group.
All infants who were referred to a single extracorporeal membrane oxygenation center and were <12 months old during a 7-year period were eligible. One year after extracorporeal membrane oxygenation, lung volume, airway conductance, maximum expiratory flow, and indices of tidal breathing were measured.
A total of 106 infants (77% of those eligible) were tested, and results were compared with those of 51 infants referred for extracorporeal membrane oxygenation as part of the original United Kingdom extracorporeal membrane oxygenation trial. Lung volume was not different, but there was a strong trend for the infants who were seen in more recent years to have better forced expiratory flow and specific airway conductance. Restricting analysis to the major subgroup (meconium aspiration) confirmed these findings. When divided into diagnostic subgroups, infants who required extracorporeal membrane oxygenation for respiratory distress syndrome or who were >2 weeks old when extracorporeal membrane oxygenation was commenced had a poorer respiratory outcome than others.
The respiratory outcome of infants who were treated beyond the tightly regulated criteria of the United Kingdom trial remains good and even shows a trend toward improvement. Certain subgroups require extracorporeal membrane oxygenation for longer and have poorer pulmonary function when followed up.
PEDIATRICS 10/2007; 120(4):e762-8. · 4.47 Impact Factor
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ABSTRACT: The role of extracorporeal membrane oxygenation (ECMO) in patients with congenital diaphragmatic hernia is still evolving. The use of ECMO is invasive with potential complications during instrumentation for cannulation and heparinization. There are no reliable predictors of outcome in patients requiring ECMO. We aimed to identify (a) the factors that could predict outcome and (b) the incidence and relation of complications during ECMO to outcome.
"Pre" ECMO (age, sex, birth weight, blood gasses, and ventilator settings) and "on" ECMO variables (mode of ECMO, use of nitric oxide, surfactant, liquid ventilation, inotropes, timing of repair, and complications on ECMO) were analyzed to identify predictors of outcome.
Fifty-two patients were included. The overall survival was 58%. Mean duration of ECMO (181 +/- 120 vs 317 +/- 156 hours, P = .001), use of nitric oxide (6 vs 10, P = .049), and renal complications (4 vs 14; P < .001) differed between survivors and nonsurvivors. The survival of patients requiring ECMO support for more than 2 weeks is significantly lower than that of patients requiring ECMO support for less than 2 weeks (18% vs 68%, P = .005). Multiple logistic regression revealed ECMO duration of 2 weeks or more and renal complications to be associated with mortality.
No pre-ECMO variable could be identified as predictor of mortality. Prolonged duration of ECMO and renal complications on ECMO were independently associated with mortality.
Journal of Pediatric Surgery 08/2007; 42(8):1345-50. · 1.45 Impact Factor
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ABSTRACT: To explore the changes in the QTc interval during mild hypothermia in neonates receiving extracorporeal membrane oxygenation (ECMO).
Twenty seven neonates (median gestation 40 weeks; range 33-41 weeks) enrolled in a pilot study of mild hypothermia were studied during the first five days of ECMO. The first group (N=7) were maintained at 37 degrees C throughout the study period. Subsequent groups (N=5) were cooled to 36 degrees C, 35 degrees C and 34 degrees C respectively for twenty four hours and the final group to 34 degrees C for forty eight hours before being rewarmed to 37 degrees C. Using a 24 h digital monitor, the QT and QTc intervals were recorded continuously during the cooling and rewarming period and validated using standard 12 lead electrocardiograms. Patients were carefully assessed clinically and routine biochemistry (including magnesium and calcium) laboratory tests measured pre ECMO and at timed intervals during cooling and rewarming.
The mean difference between the continuous digital and 12 lead ECG values for QTc was -13.3 ms. During the first 24 h of cooling, the mean (95th centile) values for the digitally measured QTc interval at 37 degrees C=431(506) milliseconds (ms); 36 degrees C=459(521) ms; 35 degrees C=445(516) ms; 34 degrees C=465(531) ms; 34 degrees C for 48 h=466(521) ms. During this period overall QTc increased by 3.12 ms (95% confidence intervals 6.17 to 0.84; p=0.04) for each degree fall in body temperature. During rewarming, there was no significant relationship between QTc and temperature change. No serious arrhythmias were during cooling. Using univariate analysis, no relationship was found between QTc and electrolytes, heart rate and blood pressure.
QTc shows significant variability in individuals, and only a small proportion of this can be explained by rectal temperature. Mild hypothermia was not associated with serious cardiac arrhythmias.
Early Human Development 05/2007; 83(4):217-23. · 2.05 Impact Factor
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ABSTRACT: To observe amplitude integrated electroencephalography (aEEG) in neonates receiving ECMO and to determine whether mild hypothermia influenced the aEEG recording.
Twenty-six consecutive neonates enrolled in a pilot study of mild hypothermia during ECMO were studied. The first group (N=6) was maintained at 37 degrees C throughout the study period. Subsequent groups were cooled to 36 degrees C (N=4), 35 degrees C (N=5), and finally 34 degrees C (N=6) respectively for 24 h and the final group (N=5) to 34 degrees C for 48 h before being rewarmed to 37 degrees C. The aEEG was recorded continuously during the first 5 days of ECMO. The aEEG was classified as normal, moderately or severely suppressed and examined for the occurrence of seizures. To assess the effect of temperature, the aEEG was compared over 12 h during the final 6 h of cooling and during the first 6 h once infants were rewarmed.
No change in aEEG amplitude was noted over the temperature range studied. Of the 26 traces obtained, 16 (62%) were normal throughout, 6 (23%) were intermittently moderately abnormal and 1 (14%) was severely abnormal. Three (11%) traces had periods of frequent seizure activity and these were not associated with clinical manifestations in two neonates. In one infant who suffered a cerebral haemorrhage, the aEEG became abnormal before cranial ultrasound abnormalities were apparent.
Continuous cerebral monitoring with aEEG is feasible during ECMO and may add information to clinical examination. Mild hypothermia to 34 degrees C for up to 48 h does not influence the aEEG suggesting that cerebral monitoring with aEEG is possible during mild hypothermia.
Early Human Development 03/2007; 83(2):69-75. · 2.05 Impact Factor
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ABSTRACT: The inflammatory response caused by extracorporeal membrane oxygenation (ECMO) is clearly visible within the first 24 h of cannulation. The inflammatory process affects all areas of the lung, even areas previously spared by the primary disease.
To compare the change in the radiographic signs of inflammatory response to ECMO between poly-methyl pentene and silicon oxygenators.
Retrospective review of neonates and adults pre- and post-replacement of silicon oxygenators with poly-methyl pentene devices. Data were collected from Extracorporeal Life Support Organisation (ELSO) registry forms and patient records. Results were analysed by quantitative and semi-quantitative methods.
There was a significant reduction in the radiographic signs of inflammatory response to ECMO, and a reduction in the time taken to revert to pre-ECMO state in the neonatal poly-methyl pentene group compared to silicon. However, there was no significant reduction in the duration of ECMO runs and the percentage survival between these groups in the neonates. In adults, there was no difference in severity of radiographic signs between groups. However, the inflammatory changes were relatively delayed in the adult poly-methyl pentene group.
Polymethyl pentene (Medos) oxygenators have reduced the host's response phenomenon 'white out' in neonates, and caused a delayed response in adults. This is most likely a consequence of smaller blood contact surface area combined with the effect of heparin coating of the oxygenator membrane. However, recovery was not a function of the type of gas exchange device used.
Perfusion 02/2007; 22(1):15-21. · 0.92 Impact Factor
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ABSTRACT: Veno-arterial extracorporeal membrane oxygenation (ECMO) is a common modality of circulatory assist device used in children. We assessed the outcome of children who had ECMO following repair of congenital cardiac defects (CCD) and identified the risk factors associated with hospital mortality.
From April 1990 to December 2003, 53 patients required ECMO following surgical correction of CCD. Retrospectively collected data was analyzed with univariate and multivariate logistic regression analysis.
Median age and weight of the patients were 150 days and 5.4 kgs respectively. The indications for ECMO were low cardiac output in 16, failure to wean cardiopulmonary bypass in 13, cardiac arrest in 10 and cardio-respiratory failure in 14 patients. The mean duration of ECMO was 143 hours. Weaning off from ECMO was successful in 66% and of these 83% were survival to hospital-discharge. 37.7% of patients were alive for the mean follow-up period of 75 months. On univariate analysis, arrhythmias, ECMO duration >168 hours, bleeding complications, renal replacement therapy on ECMO, arrhythmias and cardiac arrest after ECMO were associated with hospital mortality.On multivariate analysis, abnormal neurology, bleeding complications and arrhythmias after ECMO were associated with hospital mortality. Extra and intra-thoracic cannulations were used in 79% and 21% of patients respectively and extra-thoracic cannulation had significantly less bleeding complications (p = 0.031).
ECMO provides an effective circulatory support following surgical repair of CCD in children. Extra-thoracic cannulation is associated with less bleeding complications. Abnormal neurology, bleeding complications on ECMO and arrhythmias after ECMO are poor prognostic indicators for hospital survival.
Journal of Cardiothoracic Surgery 01/2007; 2:4. · 1.19 Impact Factor
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ABSTRACT: To report a single case of oxygenator failure caused by clot embolism originating from the bladder; and to discuss some preventative options.
A 2.5 kg neonate with a diagnosis of influenza A received veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) for cardiorespiratory support. Halfway through treatment, she underwent an elective circuit change for numerous clots in her circuit. The patient continued to consume vast quantities of platelets and developed a fatal oxygenator failure after 18 days.
Amongst the factors influencing the outcome in events of a sudden unexpected oxygenator failure are the severity of patient illness, the size of the clot relative to the size of the oxygenator, the availability of a previously primed circuit and the ease and speed of priming a new oxygenator.
There is a need for improvement in the design of small oxygenators and ECMO circuits. Adjustment of the coagulation parameters and lowering the tolerance towards clots in the circuit by electively changing them may reduce the incidence of sudden unexpected oxygenator failure. However, using a slightly larger Medos oxygenator may gain valuable time needed to arrange an oxygenator/circuit change.
Perfusion 06/2005; 20(3):177-81. · 0.92 Impact Factor
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ABSTRACT: To review the performance of polymethyl pentene versus silicone oxygenators in terms of efficiency in priming and oxygenation, oxygenator resistance, requirements for coagulation proteins and consumption of blood products, for neonatal extracorporeal membrane oxygenation (ECMO) patients.
Forty consecutive neonates were selected retrospectively pre- and post-introduction of the new polymethyl pentene (PMP) oxygenators. They formed two equal groups. After calculation of the sample size, data were collected from ELSO registry forms and patient records. Results were analysed using parametric and non-parametric tests.
Neonatal PMP (N-PMP) oxygenators were smaller, faster and easier to prime. They were less efficient than silicone oxygenators, especially in carbon dioxide elimination, and, therefore, required higher sweeps. The preservation of coagulation proteins was significantly better, but there was no reduction in the consumption of blood products, despite having less than half the surface area and significantly lower blood path resistance.
Small PMP oxygenators (Medos Hilite 800 LT) provide adequate gas exchange and offer technical advantages in terms of more efficient priming, reduced haemodynamic resistance and better control and preservation of coagulation proteins than silicone oxygenators.
Perfusion 06/2005; 20(3):129-34. · 0.92 Impact Factor
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ABSTRACT: It is likely that the imbalance between the pro- and anti-inflammatory cytokines will determine the outcome in infants with severe respiratory failure receiving extracorporeal membrane oxygenation (ECMO).
We determined if there was an imbalance between pro- and anti-inflammatory cytokines in serial bronchoalveolar lavage (BAL) fluid obtained from survivors and non-survivors of ECMO.
We therefore measured the cellular changes and the molar ratios of pro-inflammatory and anti-inflammatory cytokines in serial BAL fluid obtained from survivors and non-survivors of ECMO. Fifteen infants surviving ECMO (median age 1 day, range 1-120) and 7 who did not (28 days, range 1-402) were studied.
In the lungs of survivors, the increased proportion of airway neutrophils at presentation decreased with time and was matched by a parallel increase in percent alveolar macrophages as the infants' condition improved. The pro- and anti-inflammatory pulmonary cytokine ratios were static in the survivors. In the non-survivors, the ratio of tumour necrosis factor-alpha (TNF-alpha) against soluble TNF-receptor 1 (sTNF-R1) and soluble TNF receptor 2 (sTNF-R2) was increased at days 2-3 when compared to the survivors, but the molar ratio interleukin-1beta (IL-1beta)/soluble IL-1 receptor antagonist (sIL-1RA) was largely undetectable due to undetectable IL-1beta.
These data suggest that the infants who survive ECMO resolve their pulmonary inflammation and that in non-survivors the ratio of TNF-alpha against its receptor antagonists is increased and is associated with a poor outcome. Furthermore, this group of infants were unable to produce significant concentrations of IL-1beta.
Biology of the Neonate 02/2005; 88(4):321-7. · 1.90 Impact Factor
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ABSTRACT: We evaluated the long-term outcome of neonates receiving extracorporeal membrane oxygenation (ECMO) for congenital diaphragmatic hernia (CDH). Study design A retrospective review of all 73 neonates with CDH supported with ECMO in the United Kingdom between 1991 and 2000, with follow-up to January 2003. Information was from hospital charts and from communication with family doctors and pediatricians. Median follow-up period for survivors was 67 months.
46 infants (63%) were weaned from ECMO, 42 (58%) survived to hospital discharge, and 27 (37%) survived to age 1 year or more. A higher birth weight, higher 5-minute Apgar score, and postnatal diagnosis were "pre-ECMO" predictors of long-term survival. Comorbidity was common in long-term survivors: 13 (48%) had respiratory symptoms, 16(59%) had gastrointestinal problems, and 6 (19%) had severe neurodevelopmental problems. Only 7 children were free of significant neurodevelopmental deficit and required no further medical or surgical intervention.
Using the current referral criteria, ECMO can be used to support the sickest neonates with CDH. However, there is significant mortality in the first year of life, and long-term physical and neurodevelopmental morbidity remains in the majority of survivors.
Journal of Pediatrics 04/2004; 144(3):309-15. · 4.11 Impact Factor
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ABSTRACT: To investigate the safety and feasibility of using mild hypothermia in neonates receiving extracorporeal membrane oxygenation (ECMO). Study design A prospective, nonrandomized pilot study of 25 neonates referred for ECMO. Whole body cooling was achieved by adjustment of the temperature of the extracorporeal circuit water bath. Five groups (N=5 per group) were each studied for the first 5 days of ECMO. The first group was maintained at 37 degrees C throughout the study period. Subsequent groups were cooled to 36 degrees C, to 35 degrees C, and, finally, to 34 degrees C, respectively, for 24 hours and the final group to 34 degrees C for 48 hours before being rewarmed to 37 degrees C. Patients were carefully assessed clinically and biologically. In addition to routine laboratory tests, cytokines (IL-6 and IL-8), complement (C3a), and molecular markers of coagulation (thrombin/antithrombin III [TAT], antithrombin III, and plasmin-alpha2plasminogen) were measured.
No major clinical or circuit problems were noted during cooling or rewarming. In particular, there were no problems of bleeding or cardiac arrhythmia. No significant difference was found between groups in terms of molecular markers of coagulation, complement, cytokines, and platelet transfusions.
Applying mild hypothermia (34 degrees C) for 24 or 48 hours to neonates receiving ECMO is both feasible and safe.
Journal of Pediatrics 04/2004; 144(3):301-8. · 4.11 Impact Factor
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ABSTRACT: Severe B. pertussis infection in infants is characterized by severe respiratory failure, pulmonary hypertension, leukocytosis, and death. This retrospective case analysis highlights the course and outcome of severe B. pertussis infection treated with extracorporeal membrane oxygenation (ECMO) at a single center. Over the last decade, out of a total caseload of nearly 800 infants and children, 12 infants with severe B. pertussis have been referred for ECMO therapy to our center. All infants with pertussis infection who received ECMO therapy were less than 3 months of age at presentation and unvaccinated. There was a high mortality rate (7 of 12 infants died), which was associated with an elevated neutrophil count at presentation and multiorgan dysfunction characterized by intractable pulmonary hypertension, persistent systemic hypotension, renal insufficiency, and fits. ECMO should be offered to children with pertussis infection and respiratory failure refractory to mechanical ventilation. However, further research is required to determine the optimal management for infants receiving ECMO therapy with this disease.
Pediatric Pulmonology 11/2003; 36(4):310-5. · 2.53 Impact Factor
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ABSTRACT: Although the pharmacokinetics of midazolam in critically ill children has been described, there are no such reports in extracorporeal membrane oxygenation.
The pharmacokinetics of midazolam and 1-hydroxy midazolam after continuous infusion (50-250 microg. kg(-1). h(-1)) were determined in 20 neonates undergoing extracorporeal membrane oxygenation. Patients were randomized into two groups: group 1 (n = 10) received midazolam extracorporeally (into the circuit), and group 2 received drug via central or peripheral access. Blood samples for determination of plasma concentrations were taken at baseline, 2, 4, 6, 12, 18, and 24 h, then every 12 h. Population pharmacokinetic analysis and model building was conducted using WinNonMix (Pharsight Corporation, Mountain View, CA). The 1-hydroxy midazolam/midazolam metabolic ratio was determined as a surrogate marker of cytochrome P450 3A activity.
The parameter estimates (n = 19) were based on a one-compartment model with time-dependent change in volume of distribution. Volume (mean +/- standard error) expanded monoexponentially from the onset of extracorporeal membrane oxygenation to a maximum value, 0.8 l +/- 0.5 and 4.1 +/- 0.5 l/kg, respectively. Consequently, plasma half-life was substantially prolonged (median [range]) from onset to steady-state: 6.8 (2.2-39.8) and 33.3 (7.4-178) h, respectively. Total body clearance was determined as (mean +/- standard error) 1.4 +/- 0.15 ml. kg-1. min-1. The median metabolic ratio was 0.17 (0.03-0.9). No significant differences were observed between the two groups with respect to parameter estimates. Simulations of plasma concentration profiles revealed excess levels at conventional doses.
These results reveal significantly increased volume of distribution and plasma half-life in neonates receiving extracorporeal membrane oxygenation. Altered kinetics may reflect sequestration of midazolam by components of the extracorporeal membrane oxygenation circuit.
Anesthesiology 09/2003; 99(2):275-82. · 5.36 Impact Factor
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ABSTRACT: We measured the response of fresh heparinized human blood to recirculation through circuits made of LVA (Portex Industries, Hythe, Kent, UK), SRT (Rehau UK, Langley, Slough, UK) and Tygon S-65-HL (Norton Performance Plastics, Corby, Northants, UK), as control. Circuit construction: 1/2 in. tubing, heat exchanger (Dideco D-720P), Stockert roller pump, just underoccluded, Cincinnati Sub Zero heater, circuit volume of 500 ml. Flow 3.45 l/min, 37 degrees C. Samples: at 10 min, 1, 2, 4 and 6 h. n=5 in each group; 2/5 SRT experiments were stopped at 45 and 60 min due to overpressurization. Results: Baseline activated clotting time (ACT) of 300 s, increasing in all groups as fibrinogen fell to zero with SRT and LVA. Minimum fibrinogen was 1 g/l for Tygon. Absolute thrombocytopenia occurred (SRT and LVA 60 min and Tygon 240 min). International normalized ratio (INR) in both the SRT and LVA circuits increased, but mean increase for Tygon (0.56) was smaller than the other two materials. Plasma free haemoglobin increased in all three materials; the increase was greater in the LVA circuits compared to the control. C5b9 levels increased equally in all groups. Lactoferrin levels rose equally in all groups to a maximum at 150 min. The neutrophil counts fell, mirroring the lactoferrin. The total white cell counts also fell in all groups; in the LVA circuits, the fall was significantly lower than in the control. Rapid disappearance of platelets and fibrinogen from the blood in the SRT and LVA circuits excludes them both from extracorporeal use. Paradoxically, SRT caused the least complement activation of the three materials. This method can be used to compare biocompatibility.
Perfusion 04/2002; 17(2):125-32. · 0.92 Impact Factor
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BMJ (Clinical research ed.). 04/2002; 324(7337):610-1.
