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Biomedical subjects

R K Firmin

Publications and source records attributed to R K Firmin.

At least 19 recordsLinked to original sources
PubMed2003

Population pharmacokinetics of theophylline during paediatric extracorporeal membrane oxygenation.

AIMS: To determine the population pharmacokinetics of theophylline during extracorporeal membrane oxygenation (ECMO) from routine monitoring data. METHODS: Retrospective data were collected from 75 term neonates and children (age range 2 days to 17 years) receiving continuous infusions of aminophylline (mean rate 9.2 +/- 2.6 micro g kg-1 min-1) during ECMO. A total of 160 plasma concentrations (range 1-8 per patient), sampled at time intervals ranging from 10 h to 432 h, were included. Population PK analysis and model building were carried out using WinNonMix Professional (Version 2.0.1). Cross-validation was used to evaluate the validity and predictive accuracy of the model. RESULTS: A one-compartment model with first order elimination combined with an additive error model was found to best describe the data. Of the covariables tested, bodyweight significantly influenced clearance and volume of distribution, whereas age was an important determinant of clearance, as adjudged by the differences in the -2 x log likelihood (P < 0.005) and the residual error value. The final model parameters were estimated as: clearance (l h-1) = 0.023 x bodyweight (kg) + 0.000057 x age (days) and volume of distribution (l) = 0.57 x bodyweight (kg). The interindividual variability in clearance and volume of distribution was 38% and 40%, respectively. The residual error corresponded to a standard deviation of 3.6 mg l-1. Cross-validation revealed a median (95% confidence interval) model bias of 9.4% (2.9, 16.5%) and precision of 29.5% (24.8, 36.0%). CONCLUSIONS: The estimated clearance is significantly lower, and volume of distribution higher, than previously reported in non-ECMO patients of similar age. These differences are probably a result of the expanded circulating volume during ECMO and altered renal and hepatic physiology in this critically ill group. Large interindividual variability reflects the heterogeneous nature of patients treated on ECMO.

Bronchodilator Agents↗
PubMed2003

Pilot investigation of hypothermia in neonates receiving extracorporeal membrane oxygenation.

BACKGROUND: Infants requiring extracorporeal membrane oxygenation (ECMO) support represent a high risk group in terms of cerebral injury. Mild hypothermia both during and after cerebral hypoxic ischaemia appears to be a promising strategy for offering neuroprotection. OBJECTIVE: To investigate whether mild hypothermia was both feasible and safe in infants receiving ECMO as a prelude to any formal assessment of this approach in a randomised trial. METHODS: Twenty infants (body weight less than 5 kg) with severe cardiopulmonary insufficiency, referred for ECMO support at Glenfield Hospital, Leicester, were enrolled in this study. Twenty consecutive infants (compromising four groups of five) were studied. Baseline data were obtained from a control group who were run throughout their course at 37 degrees C. The patients in the next group were managed with a core temperature of 36 degrees C for the first 12 hours of their ECMO run, before being warmed up to 37 degrees C. After successful completion, the next group of five were cared for at 35 degrees C for the first 12 hours, and, there having been no previous complications, the final group were cared for at 34 degrees C for the first 12 hours. Patients were assessed clinically and biologically. In addition to routine laboratory tests, cytokines (interleukin 6, interleukin 8, tumour necrosis factor alpha, and C reactive protein) were measured and coagulation tests (D-dimer, thrombin-antithrombin III complex, plasmin-alpha(2)-antiplasmin complex) were performed serially for five days. RESULTS: There were no significant differences among the four groups in gestational age, birth weight, age at the time of ECMO, Apgar scores at one and five minutes, pH before cannulation, oxygenation index, duration of ECMO, and survival rate to discharge from hospital. No adverse effects of mild hypothermia were found on patient management during ECMO. Laboratory data for up to five days of ECMO also showed no difference among the four groups. CONCLUSION: Mild hypothermia (34 degrees C) for the initial 12 hours of an ECMO run is feasible.

Blood Cell Count↗
PubMed2002

Risk factors for intestinal ischaemia in cardiac surgical patients.

OBJECTIVE: Mesenteric ischaemia is an uncommon (<1%) but serious complication of cardiac surgery associated with a mortality >50%. Predictors of this complication are not well defined, and diagnosis can be difficult and prompt surgical intervention can be lifesaving. METHODS AND RESULTS: In a retrospective case-note analysis from May 1994 through to May 2000, we identified mesenteric ischaemia in 39 of 5349 consecutive patients (0.07%) undergoing cardiac surgery with cardiopulmonary bypass. By logistic multivariate analysis, we have identified six possible predictors of intestinal ischaemia: duration of cross-clamp, use of significant inotropic support, intra-aortic balloon counterpulsation for low cardiac output, need for blood transfusions, triple vessel disease and peripheral vascular disease. In all patients a combination of four predictors were present. Patients who survived this complication had surgical intervention earlier (6.4+/-3.8 h) than those who did not (16.9+/-10 h). CONCLUSIONS: The diagnosis and prompt treatment of mesenteric ischaemia post cardiac surgery requires a high degree of awareness. These predictors may be useful in alerting medical staff to the possibility of gastro-intestinal ischaemic complications after cardiac surgery particularly that early surgical intervention reduces mortality.

Cardiac Surgical Procedures↗
PubMed2002

Surgical closure of atrial septal defects in adults: effect of age at operation on outcome.

OBJECTIVE: To determine whether age has an effect on the long term outcome after surgical closure of atrial septal defects in patients aged 35 years and over. METHODS: Retrospective analysis of 89 patients (64 women) operated on between 1989 and 1999. Patients were divided into two age groups: group I (aged 35-50 years, n = 51) and group II (> 50 years, n = 38). Follow up was between 1-11 years. RESULTS: One operative death and two late deaths occurred in the study period (both in group II). Preoperatively, 29 (57%) patients were in New York Heart Association functional class III-IV in group I compared with 22 (58%) patients in group II (NS). After operation, 44 (86.2%) patients in group I were found to be in class I-II compared with 25 (71.5%, p < 0.05) in group II. Group I patients had a lower incidence of preoperative atrial fibrillation than those in group II (12 (23.5%) v 17 (43.6%), p < 0.05) and only four (7.8%) patients in group I were in atrial fibrillation requiring long term warfarin after surgery compared with 12 (34%, p < 0.05) in group II. Furthermore, echocardiography showed a greater reduction in right ventricular dimension in group I patients (mean (SD) 4.26 (0.82) v 2.71 (0.41) cm, p < 0.001) than in group II patients (4.36 (0.43) v 3.87 (0.29) cm, p = 0.21). No residual intracardiac shunts were identified during follow up. CONCLUSIONS: Surgical closure of atrial septal defects in adult patients can improve clinical status and prevent right ventricular dilatation. The greatest benefit is seen in younger patients.

Adult↗
PubMed2001

Repeatability of cellular constituents and cytokine concentration in fluid obtained by non-bronchoscopic bronchoalveolar lavage of infants receiving extracorporeal oxygenation.

BACKGROUND: Since few studies have assessed the repeatability of non-bronchoscopic bronchoalveolar lavage (NB-BAL), we compared cellular counts and cytokine concentrations in fluid obtained by standardised NB-BAL from each side of 20 intubated infants receiving extracorporeal membrane oxygenation (ECMO). METHODS: Total cell counts were obtained from 95 paired lavages and 77 pairs were suitable for differential counts and measurement of cytokine concentrations. RESULTS: Moderate correlation was noted between the two sides for most cell types including total cell counts and percentages of neutrophils and macrophages (R=0.70-0.84) and for cytokine concentrations (IL-8 R=0.78, IL-6 R=0.75, TNF-alpha R=0.64, all p< or =0.001). Using Bland-Altman analysis the mean difference between the two sides approached zero for cellular constituents (total cell counts mean difference 1.7, limits of agreement -187.5 to +190.9 x 10(4)/ml; percentage neutrophils -3.9%, -41.5% to +33.6%; percentage macrophages 3.9%, -33.8% to +41.6%) but tended to be greater on the right for logarithmically transformed cytokine measurements (IL-8: left/right ratio 0.74, limits of agreement 0.12 to 5.45, IL-6: 0.93, 0.09 to 5.87, and TNF-alpha: 0.93, 0.27 to 3.16). Using linear regression with random effects to assess the variability, only the infant's age appeared to influence the cellular results but, for cytokines, only the volume retrieved affected the variability. The magnitude of the measurements, the underlying disease, the operator's experience, days on ECMO, or survival did not affect the variability. CONCLUSION: Measurements obtained by NB-BAL need to be interpreted with caution and strongly suggest that normalisation for the dilutional effects of saline is essential.

Age Factors↗
PubMed2000

Modifying a venovenous extracorporeal membrane oxygenation circuit to reduce recirculation.

Lung rest is the primary goal of venovenous extracorporeal membrane oxygenation for severe acute respiratory failure. To achieve this there has to be adequate extracorporeal flow. This can be achieved by a two-cannula technique in most cases. In some cases, extra flow is either not achievable or causes excessive recirculation. We report 8 patients in whom we achieved adequate blood and oxygen delivery using a three-cannula technique. Five patients survived (62.5%).

Acute Disease↗
PubMed2000

In vitro evaluation of sedative drug losses during extracorporeal membrane oxygenation.

Sedative agents are routinely administered to critically ill patients, both on and off extracorporeal membrane oxygenation (ECMO), to enable patients to be comfortable and facilitate patient management. It has been observed empirically in our paediatric intensive care unit that doses of sedative drugs required to achieve desired levels of sedation in ECMO patients are far greater than those used in non-ECMO patients. These differences could not simply be accounted for by differences in patient types, clinical status or sedation levels. We therefore undertook an in vitro evaluation of drug binding in ECMO circuits. This study investigated how the polyvinyl chloride (PVC) and silicone rubber components of neonatal ECMO circuits affect drug delivery in patients through drug sorption. Phase 1 investigated drug uptake by the two polymers in static solutions of known concentrations of four commonly used sedative drugs: lorazepam, midazolam, diazepam and propofol. Phase 2 involved the setting up of a complete neonatal ECMO circuit, injecting the drug solutions pre reservoir at a flow rate of 350 ml/min and collecting samples post-oxygenator for analysis. Phase 1 results revealed significant uptake of drugs with losses in the range 40-98% and in the order propofol > diazepam > midazolam > orazepam. Phase 2 results were similar and in the first 40 min of running an ECMO circuit only 10% of propofol passed through the circuit. These results may help to explain observed clinical phenomena and raise important issues regarding drug dosing in ECMO patients.

Biocompatible Materials↗
PubMed2000

Spallation performance of extracorporeal membrane oxygenation tubing.

During the prolonged roller pump use of extracorporeal membrane oxygenation (ECMO), tubing wear generates spallation. The spallation performance of Tygon S-65-HL was measured and compared with a potential new ECMO tubing, LVA (Portex 800-500-575). Spallation was measured by on-line laser diode particle counting (HIAC) during simulated ECMO. The effects of differing levels of occlusion and pump speed were examined, as was the effect of spallation over time. The spallation produced by Tygon S-65-HL was less than that seen with LVA during 24 h of simulated ECMO (p < 0.001), and after 72 h had fallen almost to zero. Spallation with Tygon tubing increases with increasing pump speed and decreases over time. There appears to be only a weak correlation with occlusion, which is surprising. The spallation performance of Tygon S-65-HL was variable and under some conditions exceeded that of LVA. Overall, however, Tygon S-65-HL produced less spallation than LVA. Therefore, LVA cannot be recommended for clinical ECMO use.

Equipment Design↗
PubMed1999

Chronic haemoptysis as delayed complication of ventricular aneurysmectomy.

Two patients developed a ventriculo-pulmonary fistula several years after original resection of a left ventricular aneurysm. Both presented with chronic mild haemoptysis. In the first case mild haemoptysis lasted nearly 19 months, and despite a battery of non invasive and invasive investigations, diagnosis was ultimately made via exploratory thoracotomy. In the second case mild haemoptysis lasted four months and finally manifested as a large haemoptysis. Diagnosis was made preoperatively using echocardiography. We recommend the use of echocardiography when haemoptysis occurs in a patient with a previous history of ventricular aneurysm repair.

Aged↗
PubMed1999

Tubing failure during prolonged roller pump use: a laboratory study.

Little is known about the mechanical forces acting on extracorporeal circuit tubing with prolonged roller pump use during extracorporeal membrane oxygenation (ECMO). We examined the time to tubing rupture of three different materials during actual roller pump use, mean and standard deviation (SD) (SD shown in parentheses): Tygon (control) 243.7 h (175.4); LVA 121 h (14.3); and SRT 6.6 h (2.1). Failure times for both LVA and SRT were significantly different from the control (paired t-test, p = 0.02 and p < 0.001, respectively). The minimum failure times for Tygon and LVA were 99 and 101 h, respectively. We then examined Tygon under conditions of pure compression, demonstrating that even after 3.67 million compression cycles at full occlusion crack formation did not occur. If the tubing was over-occluded, cracks appeared within 24 h. Scanning electron microscopy of Tygon, which has been used during clinical ECMO, and the failure pattern during destruction testing demonstrate that shear stress and compression coexist during clinical ECMO. Use of under-occlusive pump settings could improve tubing life.

Equipment Failure Analysis↗
PubMed1998

Extracorporeal membrane oxygenation in the treatment of inhalation injuries.

Smoke inhalation is a leading cause of death in burns patients. Conventional ventilation cannot always maintain adequate tissue oxygenation. Extracorporeal membrane oxygenation (ECMO) has rarely been used in the treatment of smoke inhalation injuries. ECMO is a proven therapy in severe neonatal respiratory failure and has also been used to good effect in the treatment of children and adults. We report the cases of two children who developed severe respiratory failure refractory to maximal ventilation, one case followed smoke inhalation alone, the other followed smoke inhalation and burns. Pre-ECMO PaO2/FIO2 ratios were 6.5 and 8 kPa, respectively. The patients were treated with veno venous ECMO for 72 and 144 h, respectively. The use of ECMO for respiratory failure due to smoke inhalation and thermal injury is discussed.

Accidents, Home↗
PubMed1998

Severe acute respiratory distress syndrome secondary to acute pancreatitis successfully treated with extracorporeal membrane oxygenation in three patients.

OBJECTIVE: To review three patients who underwent extracorporeal membrane oxygenation (ECMO) for acute respiratory failure secondary to pancreatitis. SUMMARY BACKGROUND DATA: Severe acute pancreatitis often causes the acute respiratory distress syndrome (ARDS), and if ventilation is required, the mortality rate is more than 50%. If the ratio of PaO2/FiO2 falls below 100 mm Hg or the Murray lung injury score exceeds 3.5, the mortality rate rises to more than 80%. Three patients who have severe ARDS secondary to pancreatitis, who were hypoxic despite ventilation with 100% oxygen and high airway pressures, and who were all successfully treated with ECMO are reported here. The consensus here is that all three patients would have died without ECMO. METHODS: Retrospective chart review and discussion of the literature. RESULTS: Pre-ECMO data: mean PaO2/FiO2 59.3 mm Hg, mean Murray lung injury score 3.7, one patient administered 20 ppm inhaled nitric oxide. ECMO data: mean extracorporeal flow at initiation of ECMO 56.3 mL/kg per minute, all patients administered veno-venous ECMO, mean duration of ECMO 104.7 hours. All patients were successfully weaned from ECMO and extubated. One patient had a protracted hospital stay because of a colo-cutaneous fistula. All patients are long-term survivors. CONCLUSIONS: Extracorporeal membrane oxygenation proved an effective therapy for severe ARDS complicating acute pancreatitis. Extracorporeal membrane oxygenation was conducted without bleeding complications in these three patients.

Acute Disease↗
PubMed1998

Extracorporeal membrane oxygenation: potential for adults and children?

Extracorporeal membrane oxygenation is a proven therapy for severe neonatal respiratory failure. Extracorporeal membrane oxygenation for older children and adults who are failing to respond to maximal conventional therapy is more controversial, but survival figures of 50-80% can be obtained, in patients with an expected survival of 0-20% with conventional treatment.

Adult↗