Post Cardiotomy Extra Corporeal Membrane Oxygenation: Australian Cohort Review.

BACKGROUND: Over the last two decades, technological advancements in the delivery of extra corporeal membrane oxygenation (ECMO) have seen its use broaden and results improve. However, in the post cardiotomy ECMO patient group, survival remains very poor without significant improvements over the last two decades. Our study aims to report on the Australian experience, with the intention of providing background data for the formation of guidelines in the future. METHODS: Retrospective analysis of prospectively collected data from the Australian and New Zealand Society of Cardiothoracic Surgeons (ANZSCTS) Database was performed. The ANZSCTS database captures at least 60% of cardiac surgical data in Australia, annually. Data was collected on adult patients who received ECMO post cardiotomy from September 2016 to November 2017 inclusive. Transplant and primary cardiomyopathy patients were excluded. RESULTS: Of the 16,605 adult patients undergoing cardiac surgery in the 15-month period of the study, 87 patients required post cardiotomy ECMO (0.52%). The average age of the entire cohort was 56 years. Overall survival to discharge was 43.7% (n=38). Multivariable logistic regression analysis demonstrated that multiorgan failure (MOF), increasing age and longer cardiopulmonary bypass time were significant predictors of in hospital mortality. CONCLUSIONS: Post cardiotomy ECMO support is an uncommon condition. Survival in this study appears to be better than historical reports. Identification of poor prognostic indicators in this study may help inform the development of guidelines for the most appropriate use of this support modality.

A real-life experience with HeartMate III.

BACKGROUND: The HeartMate III (HM3) left ventricular assist device (LVAD) is the most recent LVAD to receive CE Mark and the Food and Drug Administration approval. It is a fully magnetically levitated pump with no reported haemolysis, pump thrombosis or pump failure in the first in-man study (a previous stody). It has now received market approval in the European Union, United States of America, and Australia. We reviewed our real-life experience with the device, to assess outcomes over the medium term. METHODS: We conducted a retrospective review of prospectively collected data for 33 consecutive patients implanted with a HM3 LVAD between November 2014 and October 2018 at The Alfred Hospital, Melbourne, Australia. RESULTS: Of the 33 patients, 31 remained alive at the census date, with only two early deaths and 11 patients transplanted. There were no pump thromboses, but there were three cases of clot ingestion (two on the right and one on the left). Seven patients required permanent biventricular assist device support. The duration of HM3 support at the time of census was a median of 196 (interquartile range, 118-386) days. CONCLUSION: This series demonstrates excellent results of the HM3 LVAD in an uncensored, real-life, consecutive group of patients in a single institution.

Cost comparison of heart transplant vs. left ventricular assist device therapy at one year.

With the worldwide shortage of donor organs, use of ventricular assist device (VAD) therapy is rapidly increasing in both the bridge to transplant and destination therapy settings. However, the high cost of VADs and VAD care is a cause for concern for policy makers who have relied on the limited supply of donor hearts to naturally cap health expenditure on heart transplantation (HTx). We sought to compare costs of the first 12 months of care of VADs vs. HTx. Single center retrospective study utilizing real generated costs over a three yr span from 2010-2012. Only patients with 12 months of costing data were included. Costs of 28 HTx patients and 24 VAD patients were analyzed. Index admission costs were more than double in the VAD group compared to the HTx group and this was driven by the procurement costs and length of stay which increased almost all aspects of in hospital care costs. Subsequent costs were six times higher in the HTx group and this was driven largely by pharmaceuticals. VAD therapy remains a very expensive treatment option for end stage heart failure patients. Device prices need to reduce substantially to make this a more widely applicable and cost effective treatment option.

Extracorporeal Life Support Bridge to Ventricular Assist Device: The Double Bridge Strategy.

In patients requiring left ventricular assist device (LVAD) support, it can be difficult to ascertain suitability for long-term mechanical support with LVAD and eventual transplantation. LVAD implantation in a shocked patient is associated with increased morbidity and mortality. Interest is growing in the utilization of extracorporeal life support (ECLS) as a bridge-to-bridge support for these critically unwell patients. Here, we reviewed our experience with ECLS double bridging. We hypothesized that ECLS double bridging would stabilize end-organ dysfunction and reduce ventricular assist device (VAD) implant perioperative mortality. We conducted a retrospective review of prospectively collected data for 58 consecutive patients implanted with a continuous-flow LVAD between January 2010 and December 2013 at The Alfred Hospital, Melbourne, Victoria, Australia. Twenty-three patients required ECLS support pre-LVAD while 35 patients underwent LVAD implantation without an ECLS bridge. Preoperative morbidity in the ECLS bridge group was reflected by increased postoperative intensive care duration, blood loss, blood product use, and postoperative renal failure, but without negative impact upon survival when compared with the no ECLS group. ECLS stabilization improved end-organ function pre-VAD implant with significant improvements in hepatic and renal dysfunction. This series demonstrates that the use of ECLS bridge to VAD stabilizes end-organ dysfunction and reduces VAD implant perioperative mortality from that traditionally reported in these "crash and burn" patients.

Right ventricular failure after implantation of continuous flow left ventricular assist device: analysis of predictors and outcomes.

Postoperative right ventricular failure is a serious complication for up to 50% of patients following LVAD insertion. Predicting RV failure is an important factor for patients as planned BiVAD support has been shown to correlate with better outcomes compared to delayed BiVAD to LVAD conversion. This retrospective study examined prospectively collected data for 101 patients implanted with an LVAD between 2003 and 2013, aiming to establish preoperative predictive factors for RVF post-LVAD insertion, analyze outcomes, and validate existing RVF scoring systems. In our cohort, 63 patients (62.4%) developed RV failure and consequently demonstrated consistently poorer survival throughout the follow-up period (log-rank p = 0.01). Multivariable logistic regression identified two significant variables: cardiac index <2.2 preoperatively despite inotropic support (OR 4.6 [95%CI 1.8-11.8]; p = 0.001) and preoperative tricuspid regurgitation (OR 8.1 [95%CI 1.9-34]; p = 0.004). Patients who developed RV failure had more complicated postoperative courses including longer ICU stay (p < 0.001), higher incidence of transfusions (p = 0.03) and re-intubation (p = 0.001), longer ventilation duration (p < 0.001), and higher incidence of returning to theater (p = 0.0008). This study found that previous validation models had only moderate correlation with our population emphasizing the need for prospective validation of these scores in the current era of continuous flow devices.

Surgical stabilisation of rib fractures: A meta-analysis of randomised controlled trials.

INTRODUCTION: Rib fixation for ventilator dependent flail chest patients has become a mainstay of management in major trauma centres. However, the expansion of rib fixation for fractured ribs beyond this remains largely in the hands of enthusiasts with the benefits in non ventilator dependent groups largely unproven. Previous meta-analyses have largely included non-randomised and retrospective data, much of which is now more than two decades out of date. We wanted to perform an updated meta-analysis including only rigorous prospective trials which were randomised. Further we wanted to include quality of life outcomes which have not been previously examined in published meta-analyses. METHODS: This meta-analysis was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and included randomised controlled trials only, of rib fixation compared to non-operative management in adult patients. RESULTS: Eight studies comprising 752 patients of whom 372 had been randomised to receive rib fixation were included. Benefits of rib fixation were identified with significant reductions in mechanical ventilation and lengths of stay (both ICU and hospital) as well as rates of pneumonia and tracheostomy. No significant benefit in quality of life at 6 months was identified. CONCLUSION: Operative intervention for rib fractures leads to significantly lower rates of pneumonia, lengths of intensive care stay and time on mechanical ventilation compared to non-operative intervention. Further study is needed to investigate quality of life improvements after rib fractures as operative rib fixation expands to non-ventilator dependent groups.

Flail chest injury-changing management and outcomes.

PURPOSE: The purpose of this study was to assess trends in management of flail chest injuries over time and to determine impact on patient outcomes. METHODS: A retrospective review of data from a prospectively collated database of all trauma patients admitted to a level 1 trauma service in Victoria was conducted. All trauma patients admitted to the hospital between July 2008 and June 2020 with an Abbreviated Injury Scale (AIS) code for flail chest injury were included. RESULTS: Our study included 720 patients, mean age was 59.5 ± 17.3 years old, and 76.5% of patients were male. Length of ICU stay decreased on average by 9 h each year. Regional anaesthesia use increased by 15% per year (0% in 2009 to 36% in 2020) (p < 0.001). Surgical stabilisation of rib fractures increased by 16% per year (2.9% in 2009 to 22.3% in 2020) (p = 0.006). The use of invasive ventilation decreased by 14% per year (70% in 2008 to 27% in 2020) (p < 0.001), and invasive ventilation time decreased by 8 h per year (p = 0.007). CONCLUSION: Over the past decade, we have seen increasing rates of regional anaesthesia and surgical rib fixation in the management of flail chest. This has resulted in lower requirements for and duration of invasive mechanical ventilation and intensive care unit stay but has not impacted mortality in this patient cohort.

Early evolution of the venom system in lizards and snakes.

Among extant reptiles only two lineages are known to have evolved venom delivery systems, the advanced snakes and helodermatid lizards (Gila Monster and Beaded Lizard). Evolution of the venom system is thought to underlie the impressive radiation of the advanced snakes (2,500 of 3,000 snake species). In contrast, the lizard venom system is thought to be restricted to just two species and to have evolved independently from the snake venom system. Here we report the presence of venom toxins in two additional lizard lineages (Monitor Lizards and Iguania) and show that all lineages possessing toxin-secreting oral glands form a clade, demonstrating a single early origin of the venom system in lizards and snakes. Construction of gland complementary-DNA libraries and phylogenetic analysis of transcripts revealed that nine toxin types are shared between lizards and snakes. Toxinological analyses of venom components from the Lace Monitor Varanus varius showed potent effects on blood pressure and clotting ability, bioactivities associated with a rapid loss of consciousness and extensive bleeding in prey. The iguanian lizard Pogona barbata retains characteristics of the ancestral venom system, namely serial, lobular non-compound venom-secreting glands on both the upper and lower jaws, whereas the advanced snakes and anguimorph lizards (including Monitor Lizards, Gila Monster and Beaded Lizard) have more derived venom systems characterized by the loss of the mandibular (lower) or maxillary (upper) glands. Demonstration that the snakes, iguanians and anguimorphs form a single clade provides overwhelming support for a single, early origin of the venom system in lizards and snakes. These results provide new insights into the evolution of the venom system in squamate reptiles and open new avenues for biomedical research and drug design using hitherto unexplored venom proteins.

Plasmin generation and fibrinolysis in pediatric patients undergoing cardiopulmonary bypass surgery.

This prospective, single-centre cohort study aimed to evaluate plasmin generation and fibrinolysis during and after cardiopulmonary bypass (CPB) surgery in a cohort of children up to 6 years of age. Blood samples were drawn at eight time points: after induction of anesthesia, before unfractionated heparin (UFH), after UFH, after initiation of bypass, before protamine, after protamine, after chest closure, and 6 h after chest closure. The study identified an increase in fibrinolysis during CPB and particularly up to 6 h afterward in children. This could be the mechanism for the significant bleeding events observed in this young population after CPB. This study establishes the foundation for future studies in this area, particularly those focusing on clinical outcomes after CPB surgery.

The quantitative and qualitative responses of platelets in pediatric patients undergoing cardiopulmonary bypass surgery.

This prospective, single-center study aimed to evaluate the platelet response during cardiopulmonary bypass (CPB) surgery in a large cohort of children up to 6 years of age. Blood samples were drawn at four time points: after induction of anesthesia, after initiation of the CPB, before protamine, and immediately after chest closure. The study recruited 60 children requiring CPB for surgical repair of congenital heart defects. The platelet count decreased throughout CPB surgery, but during the same period, platelet activity increased. The more pronounced decrease in platelet count observed in children younger than 1 year compared with that of children 1 to 6 years of age was not associated with an age-specific change in platelet activity. The overall increase in platelet function observed in this study could provide a mechanism that compensates for the decrease in platelet count. This study provides a new foundation for future studies investigating requirements of platelet supplementation in the setting of pediatric CPB surgery.

Rib fixation in non-ventilator-dependent chest wall injuries: A prospective randomized trial.

BACKGROUND: The aim of this study was to assess pain and quality of life (QoL) outcomes in patients with multiple painful displaced fractured ribs with and without operative fixation. Rib fractures are common and can lead to significant pain and disability. There is minimal level 1 evidence for rib fixation in non-ventilator-dependent patients with chest wall injuries. We hypothesized that surgical stabilization of rib fractures would reduce pain and improve QoL during 6 months. METHODS: A prospective multicenter randomized controlled trial comparing rib fixation to nonoperative management of nonventilated patients with at least three consecutive rib fractures was conducted. Inclusion criteria were rib fracture displacement and/or ongoing pain. Pain (McGill Pain Questionnaire) and QoL (Short Form 12) at 3 and 6 months postinjury were assessed. Surgeons enrolled patients in whom they felt there was clinical equipoise. Patients who were deemed to need surgical fixation or who were deemed to be too well to be randomized to rib fixation were not enrolled. RESULTS: A total of 124 patients were enrolled at four sites between 2017 and 2020. Sixty-one patients were randomized to operative management and 63 to nonoperative management. No differences were seen in the primary endpoint of Pain Rating Index at 3 months or in the QoL measures. Return-to-work rates improved between 3 and 6 months, favoring the operative group. CONCLUSION: In this study, no improvements in pain or QoL at 3 and 6 months in patients undergoing rib fixation for nonflail, non-ventilator-dependent rib fractures have been demonstrated. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.

Surgical stabilization of rib fractures versus nonoperative treatment in patients with multiple rib fractures following cardiopulmonary resuscitation: An international, retrospective matched case-control study.

BACKGROUND: The presence of six or more rib fractures or a displaced rib fracture due to cardiopulmonary resuscitation (CPR) has been associated with longer hospital and intensive care unit (ICU) length of stay (LOS). Evidence on the effect of surgical stabilization of rib fractures (SSRF) following CPR is limited. This study aimed to evaluate outcomes after SSRF versus nonoperative management in patients with multiple rib fractures after CPR. METHODS: An international, retrospective study was performed in patients who underwent SSRF or nonoperative management for multiple rib fractures following CPR between January 1, 2012, and July 31, 2020. Patients who underwent SSRF were matched to nonoperative controls by cardiac arrest location and cause, rib fracture pattern, and age. The primary outcome was ICU LOS. RESULTS: Thirty-nine operatively treated patient were matched to 66 nonoperatively managed controls with comparable CPR-related characteristics. Patients who underwent SSRF more often had displaced rib fractures (n = 28 [72%] vs. n = 31 [47%]; p = 0.015) and a higher median number of displaced ribs (2 [P 25 -P 75 , 0-3] vs. 0 [P 25 -P 75 , 0-3]; p = 0.014). Surgical stabilization of rib fractures was performed at a median of 5 days (P 25 -P 75 , 3-8 days) after CPR. In the nonoperative group, a rib fixation specialist was consulted in 14 patients (21%). The ICU LOS was longer in the SSRF group (13 days [P 25 -P 75 , 9-23 days] vs. 9 days [P 25 -P 75 , 5-15 days]; p = 0.004). Mechanical ventilator-free days, hospital LOS, thoracic complications, and mortality were similar. CONCLUSION: Despite matching, those who underwent SSRF over nonoperative management for multiple rib fractures following CPR had more severe consequential chest wall injury and a longer ICU LOS. A benefit of SSRF on in-hospital outcomes could not be demonstrated. A low consultation rate for rib fixation in the nonoperative group indicates that the consideration to perform SSRF in this population might be associated with other nonradiographic or injury-related variables. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Stability and sterility of diluted enoxaparin under three different storage conditions.

AIM: This study assessed whether enoxaparin sodium diluted to a concentration of 20 mg/mL for clinical use with 0.9% sodium chloride remained stable and sterile for up to 43 days under three different storage conditions. METHODS: Enoxaparin dilutions in polypropylene syringes were stored under three different controlled conditions of temperature and light: (i) room temperature (22-26°C) under natural light; (ii) room temperature (22-26°C) in the dark; and (iii) controlled refrigeration (2-8°C) in the dark. A weekly assay of anti-Xa and anti-IIa activity was undertaken to determine if the diluted enoxaparin preparations retained anticoagulant activity, thus remaining suitable for clinical application. RESULTS: Our findings indicate that diluted enoxaparin, when stored under the tested varied conditions of light and temperature, retained greater than or equal to 90% of baseline anticoagulant activity for anti-Xa and anti-IIa effect for up to 43 days. CONCLUSIONS: The study results are significant for families, in that they suggest that at least a month's supply of enoxaparin could be dispensed at a time, reducing the frequency of patients/families returning for supply and providing a more convenient service for paediatric patients.

Hemostatic response in paediatric patients undergoing cardiopulmonary bypass surgery.

This prospective, single-center cohort study aimed to evaluate the hemostatic response during and after Cardiopulmonary Bypass (CPB) surgery in a large cohort of children up to 6 years of age. Blood samples were drawn at eight time points: post-induction of anesthesia, pre-unfractionated heparin (UFH), post-UFH, post-initiation of bypass, pre-protamine, post-protamine, post-chest-closure, and 6 h post-chest-closure. As expected, all measures of the UFH effect increased significantly post-UFH bolus and decreased post-protamine administration. However, thrombin generation remained inhibited compared to baseline values despite the post-UFH reversal by protamine. We also demonstrate that residual UFH effect is not responsible for the ongoing inhibition of thrombin observed post-protamine administration. The significant increase in both free and total tissue factor pathway inhibitor levels during the CPB surgery might contribute to the persistent thrombin generation/endogenous thrombin potential inhibition post-protamine administration. This study makes a significant and novel contribution by investigating the physiological mechanisms behind the degree of thrombin inhibition by UFH and the residual levels of thrombin inhibition that continue despite protamine reversal and provides a new foundation for future interventional studies in the setting of paediatric CPB surgery.

Spinal cord infarction and peripheral extracorporeal membrane oxygenation: a case series.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA ECMO) is increasingly utilized in patients with cardiogenic shock due to improved technology and outcomes. Peripheral VA ECMO offers several advantages over central ECMO and is becoming increasingly popular. However, when configured via the femoral vessels, retrograde flow to the descending aorta and arch of aorta competes with antegrade ventricular output and can be associated with a watershed phenomenon and increased risk of neurologic and visceral injury. CASE SUMMARY: In this case series, we report three patients who were supported with peripheral VA ECMO for cardiogenic shock. All three were successfully weaned from peripheral VA ECMO; however, they had developed bilateral lower limb paralysis. Magnetic resonance imaging revealed spinal cord infarction in all three patients. All patients subsequently succumbed to multiorgan failure and did not survive to hospital discharge. DISCUSSION: The use of mechanical circulatory support, in particular, peripheral ECMO, has escalated with advances in technology, better understanding of cardiac physiology and improving outcomes. Spinal cord infarction is a rare but serious complication of peripheral VA ECMO support with only a few case reports published. Further studies are needed to identify the exact cause and prevention of this rare but often terminal complication. Through this series of three patients supported on peripheral VA ECMO complicated by spinal cord infarction, we review previously published reports, analyse possible mechanisms, and propose alternate management strategies to be considered in patients at risk.

Dosing and monitoring of enoxaparin (Low molecular weight heparin) therapy in children.

Low molecular weight heparins (LMWHs) are commonly used in paediatric tertiary institutions for primary prophylaxis and treatment of thromboembolic events. Despite this widespread use, the therapeutic and prophylactic guidelines for LMWH therapy in children are extrapolated from adult guidelines. In fact, there is very little information regarding the pharmacokinetics, clinical effectiveness, adverse event profile and optimal dose schedule for LMWH therapy in children. This study was designed to determine whether paediatric-specific dosage requirements for LMWH are justified, by investigating the doses required to achieve target therapeutic ranges. Patients who were treated with enoxaparin between October 2003 and July 2007 were identified for inclusion in this study. One hundred forty patients had an anti-activated factor X assay result with a total of 55 (39%) patients achieving therapeutic levels 4-6 h post dose. Children younger than 1 year required the highest dose of enoxaparin/kg and highest number of dose changes to achieve the target therapeutic range. Major bleeding occurred in one patient, equating to 0.7%, with complete clot resolution recorded in 16 (11%) patients. This study demonstrated a 2-3-fold variation in individual dose requirements for LMWH in children

Clinical use of unfractionated heparin therapy in children: time for change?

Paediatric recommendations for unfractionated heparin (UFH) management are extrapolated from adult trials, a practice that may contribute to the inferior UFH-related outcomes in children compared to adults. This is the first study to determine UFH concentration in a population of children and correlated UFH concentration with measures of UFH effect. Correlation coefficients between protamine titration (concentration) and activated partial thromboplastin time (APTT), anti- activated factor X (Xa) assay and thrombin clotting time (effect) were 0·59, 0·46 and 0·52 respectively. A protamine titration level of 0·2-0·4 iu/ml in children was not equivalent to an anti-Xa assay of 0·35-0·7 iu/ml but to an anti-Xa assay 0·17-0·85 iu/ml. In addition, use of the anti-Xa or protamine titration assays to establish an APTT therapeutic range resulted in upper limits of APTT ranges exceeding 200 s. Existing methods for determining therapeutic ranges for UFH in adult populations do not produce equivalent ranges in children. As a result, paediatric clinical guidelines that state a therapeutic range for UFH can be determined using a protamine titration assay of 0·2­0·4 iu/ml or an anti-Xa assay of 0·35-0·7 iu/ml are not based on appropriate evidence. There is an urgent need for change in our approach to the use of UFH in children.

Novel interactions between UFH and TFPI in children.

The impact of age upon therapeutic response to unfractionated heparin (UFH) in children is proposed to reflect quantitative and potentially qualitative differences in coagulation proteins across childhood. This study explores the UFH-dependent tissue factor pathway inhibitor (TFPI) release in children compared to previously published data in adults. Children <16 years of age undergoing cardiac angiography formed the population for this prospective cohort study. TFPI release was measured prior to (baseline) and at 15, 30, 45 and 120 min post-UFH dose. This study demonstrated that, whilst the immediate release of TFPI post-UFH was similar in children compared to adults, TFPI release in children remained increased and consistent for a significantly longer period post-UFH administration compared to adults. Plasma TFPI levels in children did not demonstrate an UFH concentration -dependent reduction, as has been previously reported in adults. The prolonged TFPI-mediated anticoagulant levels observed in children administered UFH may contribute to the increased rate of major bleeding reported in children compared to adults. Furthermore, we postulate that this sustained UFH-dependent increase in TFPI levels in children may influence the binding of UFH to competitive plasma proteins, such as those involved in the immunological response to UFH associated with heparin-induced thrombocytopenia.

Point-of-care monitoring of oral anticoagulation therapy in children. Comparison of the CoaguChek XS system with venous INR and venous INR using an International Reference Thromboplastin preparation (rTF/95).

Point-of-care (POC) monitoring of oral anticoagulation has been widely adopted in both paediatric and adult patients. A new POC system, the CoaguChek XS has recently been developed to measure the international normalised ratio (INR) and may offer significant advantages. The CoaguChek XS utilises a new method of electrochemical clot detection based on thrombin generation. This system has not been previously evaluated in children with reference to the laboratory gold standard, the prothrombin time using reference thromboplastin. It was the objective to compare values obtained by the CoaguChek XS system with both the venous INR and the gold standard for anticoagulant monitoring, prothrombin time with reference thromboplastin (rTF/95). To evaluate the impact of testing using the CoaguChek XS on clinical anticoagulant dosing decisions. Fifty paired venous INR and capillary CoaguChek XS results were obtained from 31 children (aged up to 16 years). The laboratory gold standard, a manual prothrombin time with reference thromboplastin (rTF/95) was additionally performed on 26 samples. Correlation between the CoaguChek XS result and the venous INR was r = 0.810. Agreement between the CoaguChek XS result and the reference INR was shown to be higher (r=0.95), in the subset analysed by this method. Correlation between the venous INR and reference INR was r=0.90. Despite changes to the methodology of testing with the CoaguChek XS POC monitoring system, the accuracy of this method when compared with both the venous INR and gold standard reference INR was satisfactory. This resulted in infrequent changes to clinical decision making regarding anticoagulation.

In vivo age dependency of unfractionated heparin in infants and children.

INTRODUCTION: Unfractionated Heparin (UFH) is used widely in paediatrics. Paediatric specific recommendations for UFH therapy are few, with the majority of recommendations being extrapolated from adult practice. In vitro studies have shown that this practice may be suboptimal. This study aimed to improve the understanding of the impact of age upon UFH response in vivo. MATERIALS AND METHODS: This prospective, observational study, conducted in the Paediatric Intensive Care Unit (PICU), included: patients 16 years or younger; treated with UFH of at least 10 U/Kg/hr. Laboratory analysis included: Antithrombin, APTT, Anti-Xa, Anti-IIa and thrombin generation expressed as the Endogenous Thrombin Potential. Results were grouped according to patient age (i.e. <1, 1-5, 6-10 and 11-16 years). RESULTS: 85 patients received an equivalent mean UFH dose with a median duration of 3 days. Antithrombin levels were decreased compared to age-related norms in children up to 11 years of age. APTT results were comparable across the age-groups. The Anti-Xa results using two different assays showed a trend for lower values in younger children. All children less than one year old recorded Anti-Xa values outside the therapeutic range for heparin therapy, for both assays. There was a trend for decreased Anti-IIa activity in younger children. Endogenous Thrombin Potential showed a significant trend for increased inhibition in older children. In vitro Antithrombin supplementation did not change the Anti-Xa or thrombin generation. CONCLUSIONS: This study confirms that, in vivo, for the same dose of UFH, the anti Xa and anti IIa effect, as well as the inhibition of endogenous thrombin potential is age dependent and that these differences are not purely AT dependent. The implication is that the anticoagulant and antithrombotic effect of a given dose of UFH differs with age. Clinical outcome studies to determine the optimal dosing for each age group are warranted.