Hypothermic Total Circulatory Arrest Research Articles

TİP-A AORT DİSSEKSİYONU CERRAHİ TEDAVİSİNDE ANTEGRAD VE RETROGRAD SEREBRAL PERFÜZYONUN KARŞILAŞTIRMASI

OBJECTIVES:
 Substantial improvement has been observed in the surgical treatment of Type-A aortic dissections in parallel with the developments in cerebral perfusion techniques. Introduction of antegrade (ACP) and retrograde (RCP) cerebral perfusion techniques with deep hypothermic total circulatory arrest (HTCA) significantly decreased neurological complications which are the most important cause of morbidity and early mortality. The incidence of temporary (TND) or permanent neurological dysfunction (PND) is still between 5.5 – 33.3%. The cerebral perfusion method is effective on this ratio, as well as factors such as age, presence of co-morbidities, emergency, diameter of the aortic arch and the ascending aorta segment that is replaced. 
 METHODS:
 In this study we have compared the operative and clinical outcomes of patients with Stanford Type-A dissection whom we operated by using antegrade and retrograde cerebral perfusion. We have also investigated which perfusion method is superior to the other, the determinants of mortality and complication rates according to the groups in order to find the determinants of mortality, and to evaluate the complication rates. The data of 115 patients who were operated for acute, subacute or chronic Stanford Type A dissection and intramural hematoma (IMH) between January 2001 – March 2013 were retrospectively evaluated.
 RESULTS: 
 No significant differences in CPB, XC, TCA, ACP, total amount of post-operative drainage, requirement of blood products, ventilation time, duration of ICU stay, hospital stay, and early mortality rates were found in our evaluation of findings and outcomes of patients in whom we either used the ACP or the RCP technique. In the multivariate analysis determinants of mortality were preoperative presence of hypertension, diabetes mellitus, extremity malperfusion, duration of CPB, and postoperative renal complications.
 CONCLUSIONS: 
 The results of our study and results of others in the medical literature regarding techniques for brain protection in open ascending and aortic arch surgery have suggested that the most effective approach to decrease the neurological complications and to obtain better outcomes may be to decrease the duration of perfusion to the possible extent.

A Successful Management of the Renal Sarcoma with an Extension of the Tumor into the Inferior Vena Cava and the Right Ventricle Progressing Multi-Organ Failure Using a Deep Hypothermic Circulatory Arrest

There has been an improvement in the prognosis of the tumor thrombi invading the inferior vena cava (IVC) and the right atrium (RA) of the renal cell carcinoma with radical nephrectomy and tumor thrombectomy with the aid of a cardiopulmonary byp ass. A 26 year old man was diag nosed with the right renal tumor with a tumor invading the right renal vein and the IVC above the right renal vein to the RA and right venticle. He was presented with dyspnea on the exertion, the ascites and the lower extremity edema due to IVC total obstruction. An acute hepatic failure occurred due to an obstruction of the hepatic vein. She received a radical nephrectomy and a removal of the tumor in the IVC and the right cardiac camber under a hypothermic total circulatory arrest using the cardiopulmonary bypass.

Integrated Cerebral Protection Combined Antegrade and Retrograde Cerebral Perfusion during Deep Hypothermic Circulatory Arrest

Aortic arch surgery requires temporary interruption of cerebral perfusion. Hypothermic circulatory arrest (HCA) is an established method of central nervous system protection for limited periods of absent cerebral blood flow. Adjuncts to increase the safe duration of circulatory arrest include either retrograde cerebral perfusion (RCP) or antegrade cerebral perfusion (ACP), with most complex aortic operations now performed using HCA with ACP. We reasoned that optimal cerebral protection might be achieved with a combination of ACP and RCP (integrated brain protection) and present an early clinical experience that supports this approach. The integrated brain protection strategy included sequential overlapping periods of RCP, ACP, and RCP during HCA. Moderate systemic hypothermia (25°C) was used. Patient data were gathered through retrospective chart review. Between 2008 and 2009, six consecutive patients underwent ascending aortic graft replacement for acute type A dissection using HCA and integrated brain protection. The mean minimum systemic temperature was 22.9 ± 1.8°C, the mean total HCA time was 34 ± 5 minutes, and the mean duration of ACP and RCP was 22 ± 6 and 7 ± 5 minutes, respectively. Patients were awake and followed commands 10.1 ± 3.4 (range, 5-13) hours after operation, and there was no evidence of temporary neurologic dysfunction. There was no operative mortality. Integrated brain protection using both RCP and ACP during HCA is a promising approach for the safe performance of complex aortic surgery and is worthy of evaluation in larger clinical series.

Deep hypothermic total circulatory arrest for internal carotid artery aneurysm extending into the cranium: experience from a developing country

Cardiopulmonary bypass is commonplace for acquired and congenital cardiac procedures. It has also stretched to facilitate complicated non-cardiac operations. Carotid artery aneurysms are treated both with surgical repair without cardiopulmonary bypass (CPB) and, occasionally, by utilizing CPB perfusion techniques. We have successfully repaired an internal carotid artery aneurysm, extending into cranium in a 30-year-old woman, by establishing deep hypothermic circulatory arrest on cardiopulmonary bypass.

Inflammatory Myofibroblastic Tumor of the Right Atrium

Cardiac inflammatory myofibroblastic tumor (IMT) is a rare entity and is associated with distinct clinical, pathological and molecular features. The clinical behavior, natural history, biological potential, management and prognosis of such tumors are unclear. We present herewith an adolescent girl who presented with similar entity involving the junction of the right atrium and the inferior vena cava (IVC) in association with thrombocytosis and IVC thrombosis leading to obstruction of blood flow. Diagnostic tools included imaging and immuno-histopathology studies. Surgical management included resection of the tumor and thrombo-embolectomy of the IVC under cardiopulmonary bypass. This case is unique due to association of complete obstruction of IVC caused by the strategic location of the tumor, thrombosis of vena cava and association of thrombocytosis. These features have not been reported yet in relation to the cardiac IMT. This report will help in better understanding and management of similar cases in terms of planning cannulation of femoral veins or application of total hypothermic circulatory arrest during cardiopulmonary bypass and prompt us to look for recurrence or metastasis during follow up using echocardiography and laboratory investigations. The possibility of IMT should be kept in the differential diagnosis of cardiac tumors especially in children and adolescents.

Giant size abdominal aortic aneurysm repair using open proximal anastomosis under hypothermic circulatory arrest: A report of two cases

Hypothermic total circulatory arrest and open proximal anastomosis techniques are not commonly used in abdominal or juxtarenal abdominal aortic aneurysm repair. Proximal aortic clamping is usually adequate for surgical repair of abdominal aortic pathologies. We present two cases of giant-sized abdominal aortic aneurysms, one was juxtarenal and one was a Crawford type IV thoracoabdominal aneurysm, that were repaired by using open proximal anastomosis under hypothermic total circulatory arrest and a transabdominal approach. This technique may be useful for both thoracoabdominal and large abdominal aortic aneurysms because it offers the opportunity to not clamp the aorta and operate in bloodless surgical field.

V-03.09: Partial circulatory arrest and cardio-pulmonary bypass for removing IVC thrombus extending up to right atrium

The standard surgical treatment for removing an IVC thrombus extending upto the right atrium involves cardio-pulmonary bypass, exsanguination and deep hypothermic total circulatory arrest. The whole process is complicated involving major risks especially deep hypothermia related coagulopathy. We have carried out two such procedures on cardio-pulmonary bypass involving a technique of partial circulatory arrest and avoidance of deep hypothermic circulatory arrest and exsanguination.

Resection of the Descending Thoracic Aorta: Outcomes After Use of Hypothermic Circulatory Arrest

Use of hypothermic circulatory arrest (HCA) for operations on the descending thoracic aorta is controversial. While deep hypothermia may provide better end-organ and spinal cord function, prolonged cardiopulmonary bypass and circulatory arrest may increase morbidity. This study assessed outcomes after use of HCA for descending thoracic aortic resection in a large cohort of consecutive patients. Hypothermic circulatory arrest was utilized if arch or extensive descending thoracic aortic resection was required, or if aortic pathology precluded cross-clamping. One hundred thirty-two patients (mean age, 61.3 years) were identified. Diagnosis included fusiform (41.2%) or saccular aneurysm (10.7%) and acute (4.6%) or chronic (38.9%) dissection. Twenty-one patients presented with rupture. Arch resection (distal arch 100, total arch 11) was required in 111 patients (84.1%). The extent of descending thoracic aortic resection (required in 94%) included proximal third in 41 patients, proximal two-thirds in 6, and complete thoracic aorta in 77. The proximal anastomosis was performed with total body HCA while the distal anastomosis was constructed with lower body HCA only (duration upper body HCA 33.7 +/- 8.0 minutes; total duration lower body HCA 71.3 +/- 24.2 minutes). Thirty-day mortality was 6.0%. Neurologic events included stroke (6.8%) and permanent lower extremity paralysis-paresis (4.5%). Temporary dialysis was needed in 7 (5.3%), though only 2 patients required permanent dialysis (1.9%). Independent predictors of a composite endpoint of death, stroke, permanent paralysis, or dialysis included duration of lower body HCA (p = 0.03) and major postoperative infection (p = 0.003). Adjunctive use of deep hypothermic circulatory arrest for descending thoracic aortic resection affords excellent preservation of end-organ and spinal cord function with acceptable rates of mortality and significant morbidity.

Time and Risk Analysis for Acute Type A Aortic Dissection Surgery Performed by Hypothermic Circulatory Arrest, Cerebral Perfusion, and Open Distal Aortic Anastomosis

Hypothermic total circulatory arrest, retrograde or antegrade cerebral perfusion, and open distal anastomosis are important stages of surgical management and cerebral protection for acute type A dissections. Among the factors that influence survival are the transfer time to hospital from the onset of symptoms, in-hospital transfer time to operation, organ malperfusion, preoperative risk factors, and intraoperative variables. The aim of this study was to analyze time and risk factors during surgical management. Between September 1996 and March 2002, a total of 26 patients with acute type A aortic dissection were operated. Sixteen patients (61.5%) were male and mean age was 49 ( 13.1 years (range: 26-68). The diagnosis was based on clinical examination, telecardiography, transthoracic echocardiography, computerized tomography, and angiography. Hypothermic total circulatory arrest, retrograde or antegrade cerebral perfusion and open distal anastomosis were used during the procedures. Operative techniques were as follows: supracoronary ascending aortic replacement (17 patients), aortic root and ascending aortic replacement with flanged composite grafting technique (5 patients), replacement of ascending aorta and hemiarcus (1 patient), aortic root and ascending aortic replacement with modified Bentall technique (1 patient), replacement of ascending aorta and arcus (1 patient), and total arcus replacement with elephant trunk technique and modified Bentall procedure (1 patient). The early postoperative mortality rate within the first 30 days was 26.9%, and the late postoperative mortality rate was 15.8%. Two patients (7.7%) developed major neurological complications during the postoperative period. Time to admission, durations of total circulatory arrest, cross-clamp, cardiopulmonary bypass, and intubation were longer, and postoperative blood loss was greater in patients who died during early postoperative period, although the differences did not reach statistical significance. Duration of total circulatory arrest was longer in patients who developed neurological dysfunction compared to patients without this complication; this difference also did not reach statistical significance. Total circulatory arrest, cerebral perfusion, and open distal anastomosis are reliable options in the surgical management of acute type A aortic dissections. With open distal anastomosis aortic arcus can be evaluated, distal anastomosis can be performed more easily, and postoperative neurological recovery is hastened. In the present study, although statistical significance could not be reached due to limited sample size, the time to admission, durations of total circulatory arrest, cross-clamp, and cardiopulmonary bypass, and the amount of postoperative chest output seem to influence postoperative survival.

Total Circulatory Arrest for the Replacement of the Descending and Thoracoabdominal Aorta

Hypothermic total circulatory arrest (TCA) in the resection and replacement of the thoracoabdominal and descending thoracic aorta is safe, will significantly decrease the incidence of postoperative renal failure, and should be preferentially performed over left heart bypass (LHB). Retrospective review case series. Large, private, urban teaching hospital. All adult patients with aortic disease that involved the distal aortic arch, the descending thoracic aorta, or the thoracoabdominal aorta who underwent resection and graft replacement of the diseased segment via LHB or TCA at our institution from 1989 to 2001 are included in this study. A total of 59 patients were evaluated: 10 had descending thoracic aneurysms, 20 had thoracoabdominal aneurysms, 22 had chronic type B dissections, 4 had acute type B dissections, and 3 had adult coarctations. In 1989 to 1994, LHB was primarily used; in 1994 to 2001, TCA was primarily used. Renal failure, 30-day operative mortality, paraplegia, and any other morbidities. A significant decrease occurred in the incidence of postoperative renal failure from 15% (3/20) in patients who underwent LHB to 0% (0/39) in patients who underwent TCA (P = .04). Furthermore, a significant decrease occurred in the 30-day operative mortality, which decreased from 20% (4/20) in patients who underwent LHB to 5% (2/39) in patients who underwent TCA (P = .04). Postoperative paraplegia decreased from 5% (1/20) in patients who underwent LHB to 2.6% (1/39) in patients who underwent TCA (P > .99). Our use of TCA in the resection and replacement of the diseased thoracoabdominal and descending thoracic aorta has produced excellent results. Our patients have experienced no postoperative renal failure and a low 30-day operative mortality. The use of TCA in this patient population is a viable option for surgeons comfortable with the technique.

Multichannel Monitoring of Cerebral Circulatory and Oxygenation Status Using Optical Topography during Deep Hypothermic Retrograde Cerebral Perfusion

In this study, we evaluated changes in the cerebral circulatory and oxygenation status during deep hypothermic total circulatory arrest (TCA) and retrograde cerebral perfusion (RCP) using optical topography, a form of multichannel near-infrared spectrophotometry, to monitor the broad area perfused by the middle cerebral artery. Seven patients underwent thoracic aortic surgery with TCA and RCP via the superior vena cava. Pressure-regulated RCP was performed under pH-stat. No postoperative neurologic complications occurred. Using optical topography, the relative changes in oxy-, deoxy-, and total hemoglobin (oxy-Hb, deoxy-Hb, total Hb) were simultaneously measured from 24 points in both hemispheres. Deoxy-Hb was used for evaluating the regional oxygenation status under RCR The values of deoxy-Hb at the beginning of RCP were regarded as the basal values, and the rate of increase in deoxy-Hb per minute (deoxy-Hb/min) was calculated at each site. Deoxy-Hb/min during TCA was also calculated. In every case, both oxy-Hb and total Hb decreased and deoxy-Hb increased during TCA. When RCP was initiated, the decrease in oxy-Hb and the increase in deoxy-Hb were attenuated. Deoxy-Hb/min was significantly lower under RCP than during TCA in all portions. There was no significant difference of deoxy-Hb/min between any portions during RCP Our results showed that the status of circulation and oxygenation might be uniform in the brain during RCP and better than that under TCA.

Comparison of Metabolic Responses to Deep Hypothermic Total Circulatory Arrest and Retrograde Cerebral Perfusion in an Experimental Model

An experimental study was designed to search the effectiveness of retrograde cerebral perfusion which is presently used as cerebral protection method for the surgery of arcus aorta. Twelve dogs were subjected to the study. Six of them were remained in total circulatory arrest at 20 °C for 60 min. Retrograde cerebral perfusion was done again at 20 °C for 1 h for the other six dogs. Tumor necrosis factor (TNF). P-selectin, Intracelluler Adhesion Molecule (ICAM), Creatine Phosphokinase (CPK-BB) and tissue Adenosine triphosphate (ATP) levels were measured, before the cardiopulmonary bypass at 37 °C and during perfusion period at 5, 60 min and 4 h. Tissue ATP level for retrograde cerebral perfusion group was 3.99±0.7 mcmol/g tissue and 2.8610.1 mcmol/g tissue for total circulatory arrest group at fourth hour (p<0.05). TNF level was significantly higher in total circulatory arrest group than retrograde cerebral perfusion group (p<0.05). The samples taken at fourth hour of reperfusion showed the TNF level was, 162.55±13.1 pcg/ml for total circulatory arrest group and this value was 12.5±3.4 pcg/ml for retrograde cerebral perfusion group. ICAM (Intracelluler Adhesion Molecule) level was higher in total circulatory arrest group (18.751±3.6 ng/ml) when compared to retrograde cerebral perfusion group (8.75±1.8 ng/ml) (p<0.05). All parameters showed that retrograde cerebral perfusion preserved the brain functions better comparing with total circulatory arrest. The time necessary for aortic surgery may be provided by the retrograde cerebral perfusion technique.

Comparison of metabolic responses to deep hypothermic total circulatory arrest and retrograde cerebral perfusion in an experimental model

An experimental study was designed to search the effectiveness of retrograde cerebral perfusion which is presently used as cerebral protection method for the surgery of arcus aorta. Twelve dogs were subjected to the study. Six of them were remained in total circulatory arrest at 20 °C for 60 min. Retrograde cerebral perfusion was done again at 20 °C for 1 h for the other six dogs. Tumor necrosis factor (TNF), P-selectin, Intracelluler Adhesion Molecule (ICAM), Creatine Phosphokinase (CPK-BB) and tissue Adenosine triphosphate (ATP) levels were measured, before the cardiopulmonary bypass at 37 °C and during perfusion period at 5, 60 min and 4 h. Tissue ATP level for retrograde cerebral perfusion group was 3.99±0.7 mcmol/g tissue and 2.86±0.1 mcmol/g tissue for total circulatory arrest group at fourth hour ( p<0.05). TNF level was significantly higher in total circulatory arrest group than retrograde cerebral perfusion group ( p<0.05). The samples taken at fourth hour of reperfusion showed the TNF level was, 162.55±13.1 pcg/ml for total circulatory arrest group and this value was 12.5±3.4 pcg/ml for retrograde cerebral perfusion group. ICAM (Intracelluler Adhesion Molecule) level was higher in total circulatory arrest group (18.75±3.6 ng/ml) when compared to retrograde cerebral perfusion group (8.75±1.8 ng/ml) ( p<0.05). All parameters showed that retrograde cerebral perfusion preserved the brain functions better comparing with total circulatory arrest. The time necessary for aortic surgery may be provided by the retrograde cerebral perfusion technique.

Aspectos da proteção cerebral em pacientes submetidos a tromboendarterectomia pulmonar com hipotermia profunda e parada circulatória intermitente

INTRODUÇÃO: A tromboendarterectomia pulmonar é utilizada como método bem estabelecido para aliviar a hipertensão pulmonar nos casos de tromboembolismo pulmonar crônico. A dificuldade que se apresenta é conciliar o tempo relativamente exíguo de parada circulatória total (PCT) hipotérmica com a completa desobstrução das artérias pulmonares, sob pena de danos neurológicos. CASUÍSTICA E MÉTODOS: No período de março de 1998 a abril de 1999 (13 meses), 8 pacientes, 5 do sexo masculino, 1 de cor negra, com idade variando entre 25 a 56 anos (média 46,2 anos) e com diagnóstico angiográfico de tromboembolismo pulmonar, foram submetidos a tromboendarterectomia pulmonar uni ou bilateral por tromboembolismo pulmonar crônico (TEP). Instalado o circuito extracorpóreo e incisada a artéria pulmonar, procede-se à PCT e, aproximadamente a cada 20 minutos de procedimento, intermitentemente, o fluxo da circulação extracorpórea (CEC) é restabelecido a 14º C por um período de 15 minutos objetivando-se a reperfusão cerebral e corpórea. Sucessivas paradas circulatórias total são realizadas e tantas quanto forem necessárias até a remoção de todos os trombos da artéria pulmonar. RESULTADOS: Não foram registrados óbitos no transoperatório. Um paciente faleceu no 30º dia de pós-operatório (PO) devido a broncopneumonia que evoluiu para sepse. Os 8 pacientes foram submetidos a CEC e PCT hipotérmica, sendo que em 5 (62,5%) foram necessárias 4 PCT e em 3 (37,5%) apenas 3 PCT, com média de 3,6 PCT. O tempo total de CEC variou de 210 a 255 minutos, com média de 225 minutos. O tempo de PCT hipotérmica variou de 58 a 88 minutos, com média de 76,7 minutos e o período de PCT por paciente variou de 18 a 24 minutos, com média de 20,5 minutos. Em todos os pacientes foram realizadas tomografias de crânio, que não revelaram nenhuma alteração anatômica, assim como o exame físico não revelou déficit motor ou rebaixamento do sensório. CONCLUSÃO: Acreditamos ser esta uma técnica promissora, capaz de oferecer tranqüilidade para o cirurgião e segurança para o paciente em termos de proteção do sistema nervoso central.

Neurological complications of congenital heart disease.

Neurological complications contribute significantly to mortality and morbidity from congenital heart disease with serious long-term consequences. Congenital heart disease has also been shown to adversely influence the neuro-developmental outcome of children. In developing countries such as India, majority of congenital heart defects remains uncorrected and major neurological complications are frequently encountered. Stroke and brain abscess are the commonest neurological complications of unoperated congenital heart disease. In developed countries the focus has now shifted to neurological complications of cardiac surgery in the very young as a result of cardiopulmonary bypass and total hypothermic circulatory arrest. A variety of neurological disturbances are now being increasingly recognized and are currently the subject of intense investigations. In this review the neurological complications of uncorrected congenital heart disease and the common neurological complications that result from operations for congenital heart disease will be discussed.

Surgery of the thoracic aorta using deep hypothermic total circulatory arrest. Are there neurological consequences other than frank cerebral defects?

Deep hypothermic total circulatory arrest has reduced primary morbidity and mortality in thoracic aortic surgery. Although frank neurological deficits have been proven to be a rare complication of this technique, the rate of subtle but irreversible neuropsychological disorders remains unknown. A total of 23 patients (15 male, 8 female) who had undergone surgery for dissection or aneurysm of the thoracic aorta using deep hypothermic total circulatory arrest (mean 25.5 min, range 10-75 min) were studied retrospectively. The mean follow-up was 17 months. The following psychometric tests were conducted: a computer-based test battery to assess tonic alertness and sustained attention, the trail making test (TMT part A and B), the Münchner Gedächtnistest and a verbal learning test. In addition, a cerebral dopamine D2 receptor scintigraphy (using the SPECT technique) was performed. For comparison, 10 healthy subjects were studied. With regard to tonic alertness, 69.6 and 30.4% were below the 50th and 10th centiles, respectively, according to age- and education-corrected standard values. The impairment in sustained attention correlated significantly with the duration of the circulatory arrest. On the tests assessing short-term memory, the patients scored 30% below their age- and education-corrected peers. In terms of long-term memory, 60.9 and 39.1% of the patients were below one and two standard deviations, respectively. Concerning speed of information processing whilst 78.3% of the patients were below the 50th and 21.7% below the 10th centile. Indicative of some persistent and functional brain alteration, the dopamine D2 receptor binding was significantly reduced when compared with healthy subjects. These data prove a substantial and chronic reduction of higher cognitive function in some of the patients who underwent cardiac surgery using deep hypothermic total circulatory arrest; this was accompanied by a depression of the cerebral dopamine D2 receptor binding.

Radical Endarterectomy of Severely Calcified Ascending Aorta Prevents Stroke During Open-heart Surgery

In ten patients (7 women), mean age 73 years, with severely calcified ascending aorta, aortic valve and coronary artery disease were surgically treated after radical endarterectomy of the ascending aorta during cardiopulmonary bypass and with or without deep hypothermic total circulatory arrest. One patient died 10 days and one 11 months postoperatively of complications which neither directly nor indirectly could be attributed to the aortic endarterectomy. The eight surviving patients are doing well after follow-up averaging 16 months. CT scans 1 year postoperatively showed no aneurysmal dilation of the ascending aorta or aortic dissection distal to the endarterectomy site. Radical endarterectomy of calcified ascending aorta thus can be performed with relatively low mortality and stroke risk and may be considered in patients undergoing valve replacement and/or coronary artery bypass grafting.

Effects of cardiac surgery on intellectual in and children

Intellectual function was evaluated by Gesell's developmental quotient (DQ) and Binet's intelligence quotient (IQ) in 161 infants and children (61 ventricular septal defects, 49 tetralogies of Fallot, 15 transpositions of the great arteries, seven atrial septal defects, five complete atrioventricular canals, five double outlet right ventricles and 19 shunt cases; average age 3.6 years) before and after cardiac surgery. There were no significant differences in preoperative DQs and IQs among the patient groups. Although average DQ scores in 21 infants with hypothermic (13–24 °C) total circulatory arrest (36–70 min) were not significantly different from the preoperative values, 13 patients with an arrest time >50 min showed a significant decrease in DQ scores. The postoperative DQ and IQ scores in patients without circulatory arrest or in shunt cases were not significantly impaired after surgery. It was concluded that cardiac surgery did not impair intellectual function in infants and children, although cerebral dysfunction might occur if circulatory arrest was >50 min.

The Pharmacokinetics of Injectable Allopurinol in Newborns With the Hypoplastic Left Heart Syndrome

The purpose of this investigation was to determine the pharmacokinetic disposition of intravenous allopurinol and its metabolite oxypurinol in neonates with the hypoplastic left heart syndrome (HLHS) and to evaluate the subsequent degree of xanthine oxidase inhibition using serum uric acid as a marker. Pharmacokinetic data were evaluated in 12 stable preoperative neonates with HLHS after a single intravenous allopurinol administration of 5 mg/kg or 10 mg/kg. Pharmacokinetic parameters were determined for elimination half-life, clearance, volume of distribution, and mean residence time. Xanthine oxidase inhibition, measured by serum uric acid reduction, was also measured. Pharmacokinetic parameters revealed no statistically significant differences between a 5-mg/kg and 10-mg/kg dose of intravenous allopurinol on elimination half-life, clearance, volume of distribution, and mean residence time. Mean serum uric acid levels were significantly reduced from baseline by 39.99 and 42.94%, respectively, in the 5- and 10-mg/kg treatment groups. The enzyme xanthine oxidase plays a key biochemical role in the generation of toxic oxygen-derived free radicals during ischemia-reperfusion conditions. Allopurinol and its active metabolite oxypurinol inhibit xanthine oxidase, and significantly reduce the conversion of hypoxanthine to xanthine and xanthine to uric acid. Cell injury may be caused by toxic oxygen free radicals produced by ischemia-reperfusion injury such as could occur during the repair of HLHS under hypothermic total circulatory arrest. We hypothesize that allopurinol may provide protection from cellular injury in this clinical context.

Cerebral metabolism and circulatory arrest: Effects of duration and strategies for protection

Hypothermic total circulatory arrest (CA) is commonly used to facilitate repair of complex congenital heart defects. However, the “safe” period of CA remains to be defined. Extended periods of hypothermic total circulatory arrest may impair cerebral metabolism and cause ischemic brain injury. This study defines the relationship between increasing durations of CA at 18 °C and cerebral metabolism, and examines the protective value of topical cooling of the head or continuous “trickle” flow (5 to 10 mL · kg −1 · min −1). Thirty-three 1-week-old piglets were randomized to six experimental groups: control; 15, 30, or 60 minutes of CA; 60 minutes of CA with topical cooling of the head; and 60 minutes of trickle flow. Animals were placed on cardiopulmonary bypass (CPB) at 100 mL · kg −1 · min −1 and cooled to 18 °C. After the experimental period of CA or trickle flow (or 60 minutes of CPB at normal flow for the control group), animals were rewarmed to 37 °C and weaned from CPB. Data were obtained before and immediately after CPB at 37 °C, and before and immediately after the experimental period at 18 °C. Parameters measured included cerebral blood flow by xenon 133 clearance, arterial and sagittal sinus blood gases, and cerebral metabolism. Hypothermic total circulatory arrest caused an impairment of cerebral metabolism that was directly proportional to CA duration ( r 2 = 0.73; p = 0.0001), and recovery of metabolic function after 60 minutes of CA improved more than 50% if the head was packed in ice. If technically feasible, CPB flow of only 5 to 10 mL · kg −1 · min −1 during hypothermia is superior to CA with respect to cerebral protection. Future studies with this model can be used to develop optimal modes of cerebral protection during neonatal heart operations.