Ivor Berkowitz

Variability in anticoagulation management of patients on extracorporeal membrane oxygenation: an international survey

Objective: The objective of this study was to determine current practices of anticoagulation in patients on extracorporeal membrane oxygenation. Design: Internet-based cross-sectional survey distributed between November 2010 and May 2011. Setting: Extracorporeal Life Support Organization-registered extracorporeal membrane oxygenation centers internationally. Participants: Extracorporeal membrane oxy genation medical directors and coordinators. Interventions: None. Measurements and Main Results: There were 121 responses from extracorporeal membrane oxy genation medical directors and coordinators at 187 Extracorporeal Life Support Organization centers with access to the survey. Eighty-four of 117 (72%) respondents reported having a written institutional extracorporeal membrane oxy genation protocol for both anticoagulation and blood product management at their institutions. Sixty-nine of 117 (59%) respondents reported use of tip-to-tip or partially heparin-bonded circuits. Unfractionated heparin was used at all centers; only 8% of respondents indicated use of alternative anticoagulation medications in the six months prior to the survey. The preferred method of anticoagulation monitoring was the serial measurement of activated clotting time, as reported by 97% of respondents. In this survey, 82% of respondents reported antithrombin III testing, 65% reported anti-factor Xa testing, and 43% reported use of thromboelastography during extracorporeal membrane oxy genation. Goal ranges for these three tests and interventions triggered by out-of-range values were found to be variable. Conclusions: Extracorporeal membrane oxy genation anticoagulation management policies vary widely by center. The majority of extracorporeal membrane oxy genation programs employ activated clotting time as the preferred anticoagulation monitoring tool. The coagulation system is also monitored using more specific markers such as antithrombin III, anti-factor Xa, and thromboelastography by a large number of centers. Future research is needed to elucidate optimal anticoagulation management and improve outcomes.

The physician's role in discussing organ donation with families

Federal Conditions of Participation from the Health Care Financing Administration (now the Centers for Medicare and Medicaid Services) introduced in 1998 require that all families be presented the option of organ and tissue donation when death is imminent. The perception that physicians were being excluded from participating in this process led to a resolution at the American Medical Association House of Delegates meeting in December 1999, calling on the American Medical Association Council on Scientific Affairs to review the Conditions of Participation “to ensure that there is no prohibition of physician involvement in the organ donation process. . ..” The number of organs procured for transplantation in the United States is insufficient to meet needs. Families’ hospital experiences significantly affect their decisions to donate organs. Discussing severe brain injury, brain death, and organ donation after brain death with families is a specialized form of end-of-life decision-making and care in the intensive care unit; however, the knowledge, skills, and attitudes necessary for physicians and nurses to promote good end-of-life decision-making are widely variable. The federal Conditions of Participation require that those making requests of families for organ donation receive specific training. They do not prohibit physician involvement in initiating organ donation requests, provided these individuals are properly trained. Physicians have an important role in caring for patients and families in these circumstances, and the care they provide is enhanced through training, attention to the special issues involved, and collaboration with organ procurement organization personnel.

Preinduction of Anesthesia in Children with Rectally Administered Midazolam

The authors evaluated the efficacy of rectally administered midazolam for preinduction (i.e., premedication/induction) of anesthesia in 67 pediatric patients, ASA physical status 1 or 2, undergoing a variety of elective surgical procedures. In phase 1, 41 children weighing 12 +/- 3 kg (range 7-20 kg) and 31 +/- 16 months (range 8-67 months) of age (mean +/- SD) received midazolam, 0.4-5.0 mg.kg-1, in an attempt to produce unconsciousness. Only one child lost consciousness (4.5 mg.kg-1). However, at all doses, inhalational induction of anesthesia was facilitated because children were tranquil and calmly separated from their parent(s). There were no clinically significant changes in arterial blood pressure, heart rate, oxyhemoglobin saturation, and end-tidal carbon dioxide concentration, 10 min after drug administration. In phase 2, 26 children weighing 17 +/- 4 kg (range 10-26 kg) and 44 +/- 19 months (range 17-84 months) months of age undergoing tonsil and/or adenoid surgery were studied to determine the optimal sedative dose of rectally administered midazolam. Patients received 0.3, 1.0, 2.0, or 3.0 mg.kg-1 of midazolam in a randomized, double-blind fashion. One third (3 of 9) of patients receiving 0.3 mg.kg-1 struggled during mask induction. All patients receiving greater than or equal to 1.0 mg.kg-1 were adequately sedated (P less than 0.008). Discharge from the postanesthesia care unit (PACU), however, was delayed (greater than 60 min) in children receiving greater than or equal to 2.0 mg.kg-1 (P less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Epinephrine Dosage Effects on Cerebral and Myocardial Blood Flow in an Infant Swine Model of Cardiopulmonary Resuscitation

Although epinephrine increases cerebral blood flow (CBF) and left ventricular blood flow (LVBF) during cardiopulmonary resuscitation (CPR), the effects of high dosages on LVBF and CBF and cerebral O2 uptake have not been examined during prolonged CPR. We determined whether log increment dosages of epinephrine would enhance LVBF and CBF and cerebral O2 uptake in an infant swine CPR model. We compared these responses with epinephrine to those with the alpha-adrenergic agonist, phenylephrine. CPR was performed in five groups (n = 6) of pentobarbital-anesthetized piglets (3.5-5.6 kg) receiving a continuous epinephrine infusion (0, 1, 10, and 100 micrograms.kg-1.min-1) or phenylephrine infusion (40 micrograms.kg-1.min-1). Plasma epinephrine concentrations increased 10-100-fold in the control group during CPR and in a stepwise manner such that concentrations were increased by more than 10(4) in the 100 micrograms.kg-1.min-1 epinephrine group. In the control group with no epinephrine infusion, LVBF decreased to less than 10 ml.min-1.100 g-1 by 5 min of CPR. With epinephrine in dosages of 10 and 100 micrograms.kg-1.min-1, LVBF at 5 min was 75 +/- 19 and 44 +/- 15 ml.min-1.100 g-1, respectively, which was significantly greater than values in the control group. With more prolonged CPR, LVBF remained significantly greater than that in the control group but only at 10 micrograms.kg-1.min-1 of epinephrine. Phenylephrine also increased LVBF for 10 min of CPR when compared with the control group. All dosages of epinephrine and phenylephrine maintained CBF close to prearrest values for 20 min of CPR. With prolonged CPR, 10 and 100 micrograms.kg-1.min-1 epinephrine resulted in significantly greater CBF than that in the control group. Incremental dosages of epinephrine did not statistically increase cerebral O2 uptake or lower the cerebral fractional O2 extraction when compared with the control group, despite the higher CBF that was generated. In this immature animal CPR model, 10 micrograms.kg-1.min-1 epinephrine is an optimal dosage for maximizing both CBF and LVBF, a dosage that substantially exceeds the current recommended epinephrine dosage for human infant CPR. In addition, for short periods of CPR, 40 micrograms.kg-1.min-1 phenylephrine increases CBF and LVBF to levels similar to those generated by high dosages of epinephrine.

Reduction of catheter-associated bloodstream infections in pediatric patients: experimentation and reality.

Objective: Few data exist on successes at reducing pediatric catheter-associated bloodstream infections (CA-BSI). The objective was to eradicate CA-BSI with a multifaceted pediatric-relevant intervention proven effective in adult patients. Design: Prospective cohort of pediatric intensive care (PICU) patients with historical controls. Setting: Multidisciplinary PICU. Patients/Participants: PICU patients with intervention targeting PICU providers. Interventions: Multifaceted intervention involving preintervention staff surveys, provider educational program, creation of central catheter procedure cart, guideline-supported central catheter insertion checklist, nursing staff empowerment to stop procedures that breached guidelines, and real-time data feedback to PICU leadership. Measurements and Main Results: We measured rate of CA-BSI per 1000 catheter days from August 2001 through September 2006. Reliable use of evidence-based best practices for insertion of central catheters in our PICU was associated with a statistically and clinically significant decrease in our CA-BSI rate for 24 months postintervention (p < .05). During a portion of this postintervention period, we experienced a dramatic increase in our CA-BSI rate that was ultimately found to be due to the introduction of a new positive displacement mechanical valve intravenous port in April 2004. After removal of this positive displacement mechanical valve, our CA-BSI rate dropped from 5.2 ± 4.5 CA-BSI per 1000 central catheter days to a rate of 3.0 ± 1.9 CA-BSI per 1000 central catheter days. Chart review of postintervention CA-BSI cases revealed that these patients acquired CA-BSI weeks after both PICU admission and after insertion of the most recent central catheter. Conclusions: Our data show that improving practices for insertion of central catheters leads to a reduction of CA-BSI among pediatric patients but not elimination of CA-BSI. More research is needed to identify best practices for maintenance of central catheters for children. In addition, our experience shows that even despite good interventions to control CA-BSI, institutions must remain vigilant to factors such as new technology with apparent advantages but short track records of use.

Improved blood flow during prolonged cardiopulmonary resuscitation with 30% duty cycle in infant pigs.

BackgroundSustained compression is recommended to maximize myocardial and cerebral blood flow during cardiopulmonary resuscitation (CPR) in adults and children. We compared myocardial and cerebral perfusion during CPR in three groups of 2-week-old anesthetized swine using compression rates and duty cycles (duration of compression/total cycle time) of 100 per minute, 60%; 100 per minute, 30%; and 150 per minute, 30%1. Methods and ResultsVentricular fibrillation was induced and CPR was begun immediately with a sternal pneumatic compressor. Epinephrine was continuously infused during CPR. Microsphere-determined blood flow and arterial and sagittal sinus blood gas measurements were made before cardiac arrest was induced and after 5, 10, 20, 35, and 50 minutes of CPR. At 5 minutes of CPR, ventricular and cerebral blood flows were greater than 25 ml · min-1 · 100 g-1 and were not significantly different between groups. When CPR was prolonged, however, myocardial and cerebral blood flows were significantly higher with the 30% duty cycle than with the 60% duty cycle. By 35 minutes, all myocardial regions had less than 5 ml · min-1 · 100 g-1 flow with the 60%1 duty cycle. In contrast, CPR with the 30% duty cycle at either compression rate provided more than 25 ml min 1 · 100 g-1 to all ventricular regions for 50 minutes. By 20 minutes, most brain regions received 50% less flow with the 60% duty cycle compared with animals undergoing CPR with the 30% duty cycle (p < 0.05). Cerebral oxygen uptake was better preserved with the 30% duty cycle. Chest deformation from loss of recoil was greater with the 60%o duty cycle compared with the 30% duty cycle. ConclusionsWe conclude that the shorter duty cycle provides markedly superior myocardial and cerebral perfusion during 50 minutes of CPR in this infant swine model. These data do not support recommendations for prolonged compression at rates of 100 per minute during CPR in infants and children.

Blood Flow during Cardiopulmonary Resuscitation with Simultaneous Compression and Ventilation in Infant Pigs

ABSTRACT: We determined whether the simultaneous chest compression and ventilation (SCV) technique of cardiopulmonary resuscitation (CPR) enhances cerebral (CBF) and myocardial (MBF) blood flows and cerebral O2 uptake in an infant swine model of CPR as it does in most adult animal CPR models. We also tested whether SCVCPR sustains CBF and MBF for prolonged periods of CPR when these flows ordinarily deteriorate. CPR was performed in two groups (n=8) of pentobarbital anesthetized piglets (3.5-5.5 kg) with continuous epinephrine infusion (10µg/kg/min). Conventional CPR was performed at 100 compressions/min, 60% duty cycle, 1:5 breath to compression ratio and 25-30 mm Hg peak airway pressure. SCVCPR was performed at 60 compressions/min, 60% duty cycle and 60 mm Hg peak airway pressure applied during each chest compression. Peak right atrial and aortic pressures in excess of 80 mm Hg were generated during CPR in both groups. At 5 min of conventional and SCV-CPR, MBF was 38 ± 7 and 46 ± 7 mL· min-1· l00 g-1 (±SE), respectively, and CBF was 15 ± 3 and 13 ± 2 mL· min-1· 100 g-1respectively. However, as CPR was prolonged to 50 min, the sternum progressively lost its recoil and the chest became more deformed. Lung inflation at high airway pressure with SCV-CPR did not prevent this chest deformation. Aortic pressure gradually declined, whereas right atrial and intracranial pressure remained constant in both groups. Consequently, MBF and CBF fell less than 10 mL· min-1· 100 g-1 and cerebral O2 uptake was markedly impaired during prolonged conventional and SCV-CPR. Therefore, SCV-CPR in an infant swine model does not enhance MBF and CBF during early CPR because intrathoracic pressure generation is already high with conventional CPR as reflected by the high right atrial pressure. In addition, SCV-CPR does not prevent the progressive chest deformation and the subsequent decline in CBF and MBF when CPR is prolonged, as is often required in pediatric resuscitation.

Organ blood flow and somatosensory-evoked potentials during and after cardiopulmonary resuscitation with epinephrine or phenylephrine.

Pure alpha-adrenergic agonists, such as phenylephrine, and mixed alpha- and beta-adrenergic agonists, such as epinephrine, raise perfusion pressure for heart and brain during cardiopulmonary resuscitation (CPR). However, with the high doses used during CPR, these drugs may directly affect vascular smooth muscle and metabolism in brain and heart. We determined whether at equivalent perfusion pressure, continuous infusion of phenylephrine (20 micrograms/kg/min) or epinephrine (4 micrograms/kg/min) leads to equal organ blood flow, cerebral O2 uptake, and cerebral electrophysiologic function. During 20 minutes of CPR initiated immediately upon ventricular fibrillation in anesthetized dogs, left ventricular blood flow was similar with epinephrine (45 +/- 9 ml/min/100 g) or phenylephrine (47 +/- 8 ml/min/100 g) infusion. The ratio of subendocardial to subepicardial blood flow fell equivalently during CPR with either epinephrine (1.23 +/- 0.06 to 0.70 +/- 0.05) or phenylephrine (1.32 +/- 0.07 to 0.77 +/- 0.05) administration. At similar levels of cerebral perfusion pressure (44 +/- 3 mm Hg), similar levels of cerebral blood flow were measured in both groups (27 +/- 3 ml/min/100 g). Cerebral O2 uptake was maintained at prearrest levels in both groups. Somatosensory-evoked potential amplitude was modestly reduced during CPR, but it promptly recovered after defibrillation. During CPR and at 2 hours after resuscitation, there were no differences between drug groups in the level of regional cerebral or coronary blood flow, cerebral O2 uptake, or evoked potentials. Therefore, with minimal delay in the onset of CPR and with equipotent pressor doses of phenylephrine and epinephrine, we found no evidence that one agent provides superior coronary or cerebral blood flow or that epinephrine by virtue of its beta-adrenergic properties adversely stimulates cerebral metabolism at a critical time that would impair brain electrophysiologic function. Moreover, epinephrine did not preferentially impair subendocardial blood flow as might be expected if it enhanced the strength of fibrillatory contractions.

Effect of adrenergic drugs on cerebral blood flow, metabolism, and evoked potentials after delayed cardiopulmonary resuscitation in dogs.

Background and Purpose Epinephrine administration during cardiopulmonary resuscitation increases cerebral blood flow by increasing arterial pressure. We tested whether potential β-adrenergic effects of epinephrine directly influence cerebral blood flow and oxygen consumption independently of raising perfusion pressure. Methods Four groups of seven anesthetized dogs were subjected to 8 minutes of fibrillatory arrest followed by 6 minutes of chest compression, ventricular defibrillation, and 4 hours of spontaneous circulation. Cerebral perfusion pressure was increased to approximately equivalent ranges during resuscitation by either 1) epinephrine infusion, 2) epinephrine infusion after pretreatment with the lipophylic β-adrenergic antagonist pindolol, 3) infusion of the a-adrenergic agonist phenylephrine, or 4) descending aortic balloon inflation without pressor agents. Results We found no difference in cerebral blood flow, oxygen extraction, or oxygen consumption during chest compression among groups. After ventricular defibrillation, depressed levels of cerebral blood flow, cerebral oxygen consumption, and somatosensory evoked potential amplitude were not different among groups. Conclusions We detected no evidence that after 8 minutes of complete ischemia, epinephrine administration during resuscitation substantially influences cerebral blood flow or cerebral oxygen consumption independent of its action of raising arterial pressure or that epinephrine has a negative impact on immediate metabolic or electrophysiological recovery attributable to its β-adrenergic activity.

Controversial Issues in Cardiopulmonary Resuscitation

Mecanismes du debit sanguin. Mecanisme de la pompe thoracique et de la pompe cardiaque. Nouvelles techniques de resuscitation. Effets des medicaments adrenergiques