Grant C. Whittlesey

Pediatric cardiac surgical ECMO: Multivariate analysis of risk factors for hospital death

BACKGROUND Extracorporeal membrane oxygenation (ECMO) has emerged as an effective technique for the mechanical support of many pediatric postcardiotomy patients with medically refractory cardiac failure. METHODS We retrospectively reviewed the records of 73 pediatric patients with congenital heart disease who were placed on ECMO support between August 1984 and February 1994. The patients were divided into groups defined by the timing of ECMO cannulation relative to the time of operation. Group 1 patients (n = 7, 9.6%) were placed on ECMO preoperatively. Group 2 patients (n = 66, 90.4%) were a heterogeneous population placed on ECMO at any interval after cardiac repair. Subgroup 2A consisted of patients (n = 17, 25.8%) who could not be weaned from cardiopulmonary bypass and were converted directly to ECMO support immediately after repair. Subgroup 2B patients (n = 49, 74.2%) were cannulated postoperatively after an initial period of clinical stability. RESULTS Hospital survival for all study patients (42/73) and for group 2 patients (38/66) was 58%. Only 4 group 2A patients (23.5%) survived their hospitalization compared with 34 group 2B patients (69.4%) (p = 0.001). Multivariate analysis identified elevated right atrial pressure after ECMO decannulation (p = 0.049) and, possibly, membership in group 2A (p = 0.061) as independent risk factors for hospital death. CONCLUSIONS Extracorporeal membrane oxygenation is most effective in salvaging pediatric cardiac surgical patients who demonstrate medically refractory hemodynamic deterioration at some interval after being successfully weaned from cardiopulmonary bypass. The right atrial pressure after extracorporeal membrane oxygenation decannulation is an independent predictor of hospital death.

Hemorrhagic complications during extracorporeal membrane oxygenation: prevention and treatment

Hemorrhage related to systemic heparinization is the major complication of extracorporeal membrane oxygenation (ECMO). Intracranial hemorrhage (ICH) is the most devastating complication. ICH developed in 13 of our 25 ECMO patients (52%). Six died, six survived with normal neurologic function, and one is severely impaired. In nine of 13 patients (69%) ECMO was discontinued when serial cranial ultrasounds showed progressive ICH. Seizures developed in six infants while receiving ECMO, and ICH developed in all. There is a correlation between hypertension and ICH. A hypertension index (hours systolic BP greater than 90/hours receiving ECMO) was 0.1 +/- 0.12 for infants without ICH and 0.37 +/- 0.28 for infants with ICH (P less than .05). ICH developed in 79% of the patients with an index greater than 0.1. Twenty neck explorations were required in the first 20 patients for incisional bleeding (mean blood loss, 21.9 +/- 18.0 mL/kg/d). We now use fibrin glue following cannulation and have done only one neck exploration in the last five patients (mean blood loss, 2.8 +/- 2.2 mL/kg/d, P less than .05). Endobronchial bleeding has responded to phenylephrine lavage and increased positive end-expiratory pressure. We have controlled pleural space bleeding with topical thrombin. None of the hemorrhagic complications encountered correlate with the activated clotting time or the amount of heparin used. There is an increased risk of hemorrhage associated with platelet counts less than 100,000/microL for 75% of a day (P less than .05) so that aggressive platelet transfusion remains important in preventing hemorrhagic complications during ECMO.

Experience with renal failure during extracorporeal membrane oxygenation: Treatment with continuous hemofiltration

We use extracorporeal membrane oxygenation (ECMO) to treat respiratory and cardiac failure in children who are unresponsive to standard ventilator and pharmacologic management. All patients have cardiac and abdominal ultrasonography prior to ECMO to identify major structural anomalies and anatomically normal kidneys. Despite this, oliguric renal failure is seen in a number of patients. Acute renal failure (ARF) developed in two of the first 20 patients we placed on ECMO and both of these patients died. Six of the last 27 patients (22%) also developed ARF and were treated with continuous hemofiltration (CH) placed in-line with the extracorporeal circuit. The technique of CH removes plasma water and dissolved solutes while retaining proteins and cellular components of the intravascular space. The duration of CH ranged from 9 to 112 hours (mean 57.5 hours). Indications for CH were hypervolemia, hyperkalemia, and azotemia. The mean serum potassium prior to CH was 5.6 (range 4.3 to 7.0) compared with 4.5 after filtration. We filtered 5 to 10 mL/kg/h and replaced it with crystalloid chosen on the basis of serum and filtrate electrolytes. These six patients had a 33% mean weight gain prior to CH. We were able to remove as much as 2,200 g in the most edematous patient with significant improvement in cardiopulmonary status. Four of the patients on CH died of their primary pulmonary or cardiac disease without specific problems related to ARF. The other two patients were successfully weaned from ECMO, extubated, and have not needed further therapy for renal failure. We conclude that CH is useful in managing the complications of oliguric renal failure during ECMO.

ECMO without heparin: Laboratory and clinical experience

To evaluate the feasibility of long-term extracorporeal membrane oxygenation (ECMO) without heparin, we placed six lambs on standard venoarterial ECMO for 71 to 96 hours. Group 1 (3 animals) was given doses of heparin to maintain activated clotting times (ACT) greater than 400 seconds. No form of anticoagulant was used for the three animals in group 2. Blood flow was maintained at 60 mL/kg/min. No histological evidence of thrombosis was noted at necropsy. ACT, prothrombin time, and partial thromboplastin time were higher in group 1, and much lower, although still above normal in group 2. Fibrinogen was significantly lower in group 2 (75 +/- 35 v 219 +/- 64 mg/dL group 1), and, although the platelet count was lower in group 2 (142 +/- 76 x 10(3)/mm3 v 225 +/- 167 x 10(3)/mm3), it was clinically acceptable. These results encouraged us to discontinue heparin when faced with severe hemorrhage in four patients on ECMO, rather than withdraw support at a time when there was little chance of survival. Heparin was discontinued for 10.5 +/- 6 hours. The mean ACT was reduced from 220 +/- 23 seconds to 144 +/- 22 seconds. One patient, who required repair of gastric necrosis while on ECMO following repair of a congenital diaphragmatic hernia, survived and had a decrease in blood loss from 2 to 0 mL/kg/h after the heparin was discontinued. One of the three patients who died had an autopsy with no evidence of thrombosis. We conclude that it may be reasonable to discontinue heparin in the face of life-threatening hemorrhage while on ECMO.

Extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation has now evolved into standard therapy for patients unresponsive to conventional ventilatory and pharmacological support. This article presents a clinical review of extracorporeal life support and its application to neonatal and pediatric patients as well as children requiring circulatory support after open heart surgery.

Regional blood flow during extracorporeal membrane oxygenation in lambs

To determine changes in blood flow to different organs during extracorporeal membrane oxygenation (ECMO), the authors performed venoarterial ECMO in four young lambs for 71-96 hr (Group 1). Macroaggregated albumin microspheres labeled with technetium 99m were injected through the perfusion cannula before termination of ECMO to determine percent of blood flow by measuring radioactivity from the microspheres lodged in specific organs. The control group (Group 2) consisted of three animals not on bypass; injections were made through a catheter placed in the left ventricle. Relative coronary blood flow from the perfusion cannula was significantly less than relative coronary blood flow in the control group, possibly because of cannula location. Renal flow from the perfusion cannula also was decreased. Contrary to observations in rabbits, cerebral perfusion did not decrease in the bypass group despite ligation of the carotid artery and the external jugular vein. There were no statistically significant differences between the two groups in the relative blood flow to other organs. The authors conclude that ECMO may significantly alter myocardial and renal perfusion, with minimal effects to other organs.

Effective control of chylous ascites: An alternative approach

Complete control of chylous ascites was achieved by creating a circuit for extracorporeal recirculation of the ascites fluid from the peritoneal cavity to the superior vena cava. A hemofilter was incorporated into the circuit to remove water and electrolytes while returning protein, fat, and white cells. This avoided the associated loss of calories. This system could be applied to other forms of refractory ascites.

Clotting parameters in patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion and instrumentation.

Thirty-six patients, 9 males and 27 females, average age 13.2 years, undergoing posterior fusion and segmental instrumentation surgery for idiopathic adolescent scoliosis were studied for abnormalities of platelet count (PC), prothrombin time (PT) and partial thromboplastin time (PTT). Intraoperative and immediate postoperative values were obtained at 2, 4, 6, 12, 24, and 48 hours. All patients showed diminution of platelet counts during the study period, but mean values were reduced below normals only at 4 hours after operation. The PT was significantly elevated in all patients intraoperatively and for the first 24 hours postoperatively, with return to normal by 48 hours. The PTT levels were essentially unaffected at any time.

Evaluation of contrast media for bronchography.

Background. Bronchography is occasionally needed for the evaluation and management of some congenital pulmonary anomalies as well as some acquired diseases, usually of the tracheo- bronchial tree. There is currently no effective, approved contrast agent for this imaging tech- nique. Objective. We evaluated five agents (barium sulfate, iohexol, propyliodone oily, propyliodone aqueous, and perflubron) in terms of image quality, histologic changes, and effects on hemodynamics, blood gases, and standard laboratory tests in New Zealand White rabbits. Materials and methods. Animals were anesthetized and intubated. Each contrast agent (0.25 ml/kg) was administered intratracheally. Three animals in each group had intravenous lines placed for blood sampling and blood pressure monitoring and were sacrificed at 1 h. An additional three animals for each agent were sacrificed at 24 h and 1 week after imaging. Blood samples were taken immediately before contrast instillation and at 1 h postbronchography. Fluoroscopic images were recorded on standard VHS video tape and evaluated in blind fashion. Segments of lung tissue and bronchi were obtained for histologic examination. Results. Necrosis and/or inflammatory infiltrates were noted in 78 % of the bronchograms performed with propyliodone aqueous, 67 % with propyliodone oily, 55 % with perflubron, and 33 % with iohexol 120, 240 and 350. No histologic damage was observed with barium. The propyliodones gave the best-quality imaging results and the most histologic changes. Iohexol, in any concentration, gave the least acceptable images and a moderate number of histologic changes. Barium sulfate demonstrated acceptable images with virtually no histologic changes. Conclusion. From the histologic and imaging results, barium is the best available contrast material for bronchography.

Thermal, operational, and storage stability of immobilized carbonic anhydrase in membrane lungs.

The significant improvement in CO2 removal rates from blood through membrane lungs with EMCO and ECCO2R is achievable by means of the immobilization of carbonic anhydrase (CA) onto the membrane surface. The practical application of this technology requires that the enzyme be maintained for long periods without loss of activity. Thus, studies were performed to evaluate the thermal, operational, and storage stability of CA in a cellulose nitrate-encapsulated, silicone rubber membrane-immobilized form. Cellulose nitrate microcapsules containing 1000 micrograms/ml CA were prepared using a modified version of the method of Chang, and immobilized onto a 0.06 m2 section of commercial silicone rubber membrane material. The extent of enzyme activity in free solution and in the encapsulated form was determined after long-term storage at 4 degrees C, 37 degrees C, and 50 degrees C. Likewise, in an in vitro test circuit, CO2 removal efficiency in both CA treated and untreated membrane lungs was measured for extended time periods of 10 hr over a 10 day period. The thermal stability tests showed a significantly greater degree of retained enzyme activity in the encapsulated form, over the free enzyme in solution, at all temperatures. This was especially evident at higher temperatures and when the enzyme was stored for extended periods. In the operational stability tests, the CO2 removal efficiency of the treated membrane was not degraded, and stayed significantly higher than the untreated membrane for extended time periods. This further illustrates the potential for the use of the immobilized enzyme, carbonic anhydrase, for improved CO2 removal efficiency.