ANESTHESIOLOGY AND PAIN MANAGEMENT 1. Kelley SD, Ramsay MA. Respiratory rate monitoring: characterizing performance for emerging technologies. Anesth Analg 2014;119(6): 1246–1248. 2. Kudenchuk PJ, Brown SP, Daya M, Morrison LJ, Grunau BE, Rea T, Aufderheide T, Powell J, Leroux B, Vaillancourt C, Larsen J, Wittwer L, Colella MR, Stephens SW, Gamber M, Egan D, Dorian P; Resuscitation Outcomes Consortium Investigators. Resuscitation Outcomes Consortium-Amiodarone, Lidocaine or Placebo Study (ROC-ALPS): Rationale and methodology behind an out-of-hospital cardiac arrest antiarrhythmic drug trial. Am Heart J 2014;167(5):653–659.e4. 3. Ramsay M. Breathing is good. J Clin Monit Comput 2014 Jul 26 [Epub ahead of print]. 4. Ramsay M. Listening to breathing again! J Clin Monit Comput 2014; 28(6):559–560. 5. Ramsay M. Th e biological cost of the depression of consciousness. Revista Colombiana de Anestesiologia 2014 Dec 13 [Epub ahead of print]. 6. Ramsay MAE, Newman KB, Jacobson RM, Richardson CT, Rogers L, Brown BJ, Hein HAT, De Vol EB, Daoud YA. Sedation levels during propofol administration for outpatient colonoscopies. Proc (Bayl Univ Med Cent) 2014;27(1):12–15. 7. Ramsay MAE, Newman KB, Leeper B, Hamman BL, Hebeler RF Jr., Henry AC, Kourlis H Jr., Wood RE, Stecher JA, Hein HAT. Dexmedetomidine infusion for analgesia up to 48 hours after lung surgery performed by lateral thoracotomy. Proc (Bayl Univ Med Cent) 2014;27(1):3–10. 8. Stiell IG, Brown SP, Nichol G, Cheskes S, Vaillancourt C, Callaway CW, Morrison LJ, Christenson J, Aufderheide TP, Davis DP, Free C, Hostler D, Stouff er JA, Idris AH; Resuscitation Outcomes Consortium Investigators. What is the optimal chest compression depth during outof-hospital cardiac arrest resuscitation of adult patients? Circulation 2014;130(22):1962–1970.

Study Objective: The objective of this study was to examine the utility of the transesophageal echo-Doppler device in evaluating hemodynamic changes during laparoscopic cholecystectomy.Design: This was a prospective, controlled, observational open study.Setting: The study took place in a university hospital.Patients: Twenty patients with ASA physical statuses II and III undergoing laparoscopic cholecystectomy were enrolled into the study.Interventions and Measurements: A standardized general anesthetic and surgical technique was used for all patients. Similar depth of hypnosis (using bispectral index monitoring) was maintained in all patients. Hemodynamic parameters including mean arterial pressure (MAP), cardiac index (CI), left ventricular (LV) ejection time interval indexed to the heart rate, maximum acceleration, peak velocity, and systemic vascular resistance (SVR) were recorded at predetermined intervals: before incision, after peritoneal CO2 insufflation and head-up tilt, every 10 minutes thereafter, and after deflation of the abdomen and return to supine position.Main Results: The transesophageal echo-Doppler probe placement was achieved in 3 to 5 minutes in all patients, and the probe position was maintained after creation of pneumoperitoneum and change in positioning. Induction of pneumoperitoneum and head-up tilt resulted in a significant increase in MAP and SVR (P <.05) that remained higher until deflation. The CI, LV ejection time interval indexed to the heart rate (a measure of LV filling), and maximum acceleration (a measure of contractility and global ventricular function) remained stable.Conclusions: The transesophageal echo-Doppler device can be used during laparoscopic cholecystectomy. The LV function, as determined by measurement of CI and maximum acceleration, was preserved during laparoscopic cholecystectomy despite significant increases in afterload (ie, MAP and SVR). (c) 2005 Elsevier Inc. All rights reserved.

Objective We undertook this study to understand the factors at our transplant center that contribute to patients' return to the ICU after their liver transplant and their initial discharge from that unit. Patients who, after liver transplantation, fail discharge from the Intensive Care Unit (ICU) and must be readmitted to that unit may well utilize many more resources than those patients who are well enough to stay out of the ICU. Design A retrospective review of a prospectively maintained liver transplant research database followed by a retrospective review of (a subgroup) patient charts and contemporaneous controls. Setting A large metropolitan tertiary care center and adult liver transplant center. Patients A total of 1,197 consecutive adult patients who underwent their initial liver transplantation from 1984 to 1996. Intervention Readmission to the intensive care unit after adult liver transplantation and discharge from that unit. Main Results Only recipient age, pretransplant synthetic function labs (protime and albumin), bilirubin levels, and intraoperative blood product requirements could be statistically linked to the group requiring ICU readmission. The primary etiology for ICU readmission was cardiopulmonary deterioration. Readmission was associated with significantly lower patient and graft survivals. A detailed review of 23 patients transplanted from October 1994 to June 1996 was made, with special emphasis on cardiopulmonary status (hemodynamics, respiratory variables, and chest radiograph findings). This subgroup was compared with 30 temporally matched controls who were not readmitted to the ICU. Intravascular fluid overload and lower inspiratory capacity were significant factors related to ICU readmission. Readmitted patients had a longer hospitalization with higher hospital charges than the control group. Conclusions We conclude that the most important means of preventing ICU readmission in liver transplantation patients is to optimize cardiopulmonary function and status. Close monitoring of fluid balance to avoid hypervolemia is essential. Readmitted patients have a greater resource utilization and have lower survival rates.

S418 INTRODUCTION: There is evidence that patients with hepatic cirrhosis have elevated levels of exhaled nitric oxide (NO). [1] This study was designed to examine the effect of orthotopic liver transplantation (OLT) on the perioperative concentrations of exhaled NO in patients with end-stage liver disease. METHODS: After IRB approval and informed consent, 4 patients undergoing orthotopic liver transplantation were studied. Exhaled NO concentrations were measured using a rapid response chemiluminescence analyzer (Sievers Instruments Inc. Boulder, Co). A restricted exhaled breath technique was utilized. Contamination by nasopharyngeal NO was excluded by using a constant exhalation pressure of 20 torr and 46 ml/s exhalation flow rate. Initial measurements were taken just prior to induction of anesthesia. Post-transplant measurements were taken daily after completion of surgery with the patient extubated. Laboratory data (PT, AST, ALT) were also obtained to determine if signs of graft dysfunction affected levels of exhaled NO. RESULTS: All patients maintained elevated levels of exhaled NO post-operatively, however, patients 1 and 3 displayed signs of acute cellular rejection. In both of these patients the exhaled NO concentrations peaked at a level above that measured in the preoperative period. Patient 1 increased from 38.4ppb to 49ppb and patient 3 increased from 35.3ppb to 42.3ppb, respectively. See Table 1.Table 1: Exhaled NO Concentrations in extubated OLT patients. (Normal exhaled NO value for a healthy individual [similar]10ppb.)DISCUSSION: Nitric oxide is hypothesized as being the mediator of peripheral vasodilation in patients with cirrhosis. Hepatocytes and Kuppfer cells have been shown to produce excessive amounts of NO in cirrhotic livers [2]. Because NO is thought to be rapidly inactivated by the circulating hemoglobin, it is likely that most of the exhaled NO is the result of excessive local production of NO by the lung, rather than the liver. Vascular and bronchial endothelial cells probably produce this NO and that would account for the maintained increased levels of exhaled NO after implantation of a new liver graft. Recent studies, however, have shown that some NO may not be deactivated by hemoglobin but is instead transported as s-nitrosyl hemoglobin [3-4]. This may then be circulated directly to the lungs where it is released as exhaled NO. If this is true, then the liver hepatocyte function could be a component of exhaled NO concentrations. This preliminary data does show some trends of an increase in exhaled NO with early signs of graft dysfunction. Further studies should be able to demonstrate if concentrations of exhaled NO are a reliable marker of graft dysfunction.

955 Introduction: Severe pulmonary hypertension (PHT) in conjunction with end-stage liver disease (ESLD) is a significant perioperative risk to patients undergoing orthotopic liver transplantation (OLT) (1). In a previous study, only 2 of 7 patients with PHT had a long-term survival after OLT. The remaining 5 patients died as a result of right heart failure (2). In a prospective study, patients with severe portopulmonary hypertension requiring OLT were administered epoprostenol and nitric oxide (NO) prior to OLT to determine if the PHT could be lowered to a mean pressure of less than 35mmHg. If the patient responded to either therapy and had good RV contraction, OLT was undertaken. Post-transplantation, an epoprostenol infusion continued until PAP normalized. Method: Five patients were diagnosed with severe portopulmonary hypertension, either during evaluation for OLT or at the time of transplantation. A trial of inhaled NO up to 40ppm was performed and then an infusion of epoprostenol was started at 5 ng/kg/hr and increased to the maximum tolerated by the patient. Transplantation was only performed if mean PAP ≤ 35mmHg was achieved and RV function was assessed normal on echocardiogram. Post-operatively, the epoprostenol infusion was maintained until PAP was in the normal range and RV function was assessed by echocardiogram as normal. Results:(Table)TableConclusion: Prior to instituting a protocol requiring the reversal of MPAP to ≤ 35 mmHg before transplantation post-operative mortality was 71% (5 of 7 patients). After instituting this protocol, using chronic epoprostenol infusion perioperatively and NO therapy, 100% of patients (5 of 5) have retained good RV function and quality of life, and MPAP have not increased.

(M. A. E. Ramsay) Chief of Anesthesiology, Departments of Anesthesiology and Pain Management, Baylor University Medical Center, and Clinical Professor, University of Texas Southwestern Medical Center.(Spikes) Transplant Anesthesia Fellow, Departments of Anesthesiology and Pain Management, Baylor University Medical Center and the University of Texas Southwestern Medical Center.(East) Attending Staff Cardiologist, Department of Cardiology, Baylor University Medical Center.(Lynch) Respiratory Therapist, Department of Respiratory Medicine, Baylor University Medical Center.(Hein) Attending Staff Anesthesiologist, Departments of Anesthesiology and Pain Management, Baylor University Medical Center, and Clinical Professor, University of Texas Southwestern Medical Center.(K. J. Ramsay) Anesthesia Research Assistant, Department of Anesthesiology and Pain Management, Baylor University Medical Center.(Klintmalm) Director of Transplantation Services, Baylor Institute of Transplantation Services, Baylor University Medical Center.END-STAGE liver disease is associated with a hyperdynamic circulatory state. The pathophysiologic changes include a decreased systemic vascular resistance, an increased cardiac index, and portal hypertension together with the formation of vascular shunts. [1]These changes may be the result of an increased production of NO synthase and the resulting increase in endogenous nitric oxide (NO) causing profound vasodilation. [2]This hypothesis is further supported by the demonstration of an increased concentration of NO in the exhaled breath of patients with severe liver cirrhosis. [3,4]The pathophysiologic changes in the lung may include vascular dilatations, arteriolar wall thickening, and vascular lumen occlusion from thromboembolism. If vascular dilatations predominate in the lung, then hepatopulmonary syndrome (hypoxemia associated with hepatic dysfunction and intrapulmonary vascular shunts) may result. [5]If vascular wall thickening or occlusion predominates, then pulmonary hypertension may develop as a result of increased resistance to blood flow. All three pathologic states have been shown to exist simultaneously. [6]Pulmonary hypertension associated with end-stage liver disease may be found in up to 8.5% of patients presenting for liver transplantation. [7]It may be defined as a mean pulmonary artery pressure (PAP) of greater than 25 mmHg with a normal pulmonary artery occlusion pressure (PAOP) and pulmonary vascular resistance (PVR) of greater than 120 dynes [middle dot] s (-1)[middle dot]-5. [8]Pulmonary hypertension may further be divided into severe (mean PAP > 45 mmHg), moderate (mean PAP > 35 mmHg), or mild (mean PAP > 25 mmHg). [7]Patients with moderate and severe pulmonary hypertension have a reduced 3-year survival after liver transplantation compared to patients presenting with normal or mild pulmonary hypertension. [7]Therefore, we endeavor to reverse pulmonary hypertension before submitting a patient to liver transplantation in an attempt to improve outcome.Our previous experience and other reports have shown that inhaled NO does not reverse pulmonary hypertension associated with liver disease. [9,10]This is not entirely unexpected, because patients with severe cirrhosis have been reported to have increased levels of endogenously produced NO. [3,4]We now describe a patient with produced NO. [3,4]We now describe a patient with end-stage liver disease who responded to inhaled NO on several occasions.This case report describes a patient in whom the combination of inhaled NO and an infusion of epoprostenol were used together to successfully control pulmonary hypertension perioperatively in a patient undergoing liver transplantation.The patient was a 62-yr-old, 60-kg woman with end-stage liver disease as a result of hepatitis C, the Child-Turcotte Pugh Score was 10. A liver biopsy revealed severe cirrhosis, and she had a clinical course or progressive fatigue, muscle wasting, encephalopathy, and asymptomatic esophageal varices. Prothrombin time was 13.2 s, total bilirubin concentration was 1.6 mg/dl, serum aspartate aminotransferase and serum alanine aminotransferase concentrations were 71 IU/l and 55 IU/l, respectively (normal values 5-50 IU/l and 5-40 IU/l). A chest radiograph showed a prominent pulmonary artery and the electrocardiogram (ECG) showed a right-side heart strain pattern. Therefore, echocardiography was performed and revealed evidence of pulmonary hypertension. A right-side heart catheter was placed and a PAP of 63/18 mmHg (mean 38 mmHg), a pulmonary vascular resistance of 527 dynes [middle dot] s-1[middle dot] cm-5, a PAOP of 5 mmHg, and a cardiac output of 4.5 l/min were recorded. After Institutional Review Board approval and informed patient consent, inhaled NO was administered via a face-mask and nonrebreathing circuit from an I-NOvent (Ohmeda, Liberty Corner, NJ) system. Nitric oxide was increased by increments of 10 ppm and at a concentration of 40 ppm inhaled NO, PAPs decreased to 47/13 mmHg (mean 28 mmHg), and the PVR decreased to 383 dynes [middle dot] s (-1)[middle dot] cm-5. The PAOP remained at 5 mmHg, and cardiac output was 4.8 l [middle dot] min-1. At cessation of the trial of NO, PAPs reverted to baseline levels during the next 30 min. The inhaled NO trial was repeated the next day with similar results (see Table 1).An infusion of epoprostenol was then started at 2 ng [middle dot] kg-1[middle dot] min-1and increased to 7 ng [middle dot] kg-1[middle dot] min-1, the highest dose tolerated by the patient because of headaches. Mean PAPs were maintained between 32-35 mmHg before removing the pulmonary artery catheter. The patient received a continuous infusion of epoprostenol for 3 weeks before a donor liver became available. At arrival in the operating room for liver transplantation, PAPs of 46/13 mmHg (mean 29 mmHg), a PVR of 193 dynes [middle dot] s-1[middle dot] cm-5, and a PAOP of 16 mmHg were noted. Inhaled NO was again instituted via a facemask and PAPs further decreased to 40/13 mmHg (mean 24 mmHg), PVR decreased to 176 dynes [middle dot] s-1[middle dot] cm-5, and PAOP decreased to 13 mmHg. Nitric oxide was discontinued and the PAPs returned to baseline levels, but the epoprostenol infusion was continued.At reperfusion of the liver graft, PAPs increased to 46/23 mmHg (mean 34 mmHg), PVR increased to 320 dynes [middle dot] s-1[middle dot] cm-5, and PAOP decreased to 10 mmHg. At the same time, the ST segment on lead II of the ECG was noted to be acutely increased to 5 mm. Inhaled NO at 40 ppm was administered to reverse the pulmonary hypertension, and simultaneously a rapid resolution of the ECG changes was noted. The rest of the procedure was uneventful, and the NO was weaned off with a mild elevation in PAP to a mean pressure of 32 mmHg.Posttransplantation in the intensive care unit, the PAPs remained increased at a mean pressure of 35 mmHg; therefore, the epoprostenol infusion was continued. The patient went home on the tenth postoperative day, still receiving an epoprostenol infusion at 9 ng [middle dot] kg-1[middle dot] min-1. At 3 months postoperatively, the patient was reevaluated by echocardiography and noted to have near-normal PAPs (mean 25 mmHg). A slow weaning of the epoprostenol infusion was commenced.It is intriguing as to why this patient responded to inhaled NO when previous patients with end-stage liver disease have not shown a response. [9,10]However, a single case report showed an intraoperative response to inhaled NO in a patient undergoing liver transplantation who had severe pulmonary hypertension. [11]Inhaled NO may have caused the reversal of an acute pulmonary vasoconstrictive episode after the perfusion of the lung by cold blood from the donor organ. The severe ischemia noted on the ECG may have been the result of acute right-side heart strain caused by a sudden increase in afterload to the right ventricle, although the PVR did not reach previously increased levels. The ischemia may have been induced by coronary vasospasm caused by the placement of the cold donor organ directly beneath the heart. [12]The rapid resolution of this episode may not be related to the NO therapy, or it may have been the result of the reduction in right ventricular afterload by NO. The transport of NO by red corpuscles combined with hemoglobin as S-nitrosohemoglobin and its release of NO on deoxygenation in the coronary artery, causing direct vasodilatation, has been suggested. [13]The concept, that inhaled NO can be delivered to the distant microvasculature, recently has been confirmed in the feline model. [14]The positive preoperative response to inhaled NO in this patient may have been the result of a lack of increased levels of endogenous NO because the typical hyperdynamic circulation of severe liver cirrhosis did not exist in this patient. The measured cardiac outputs were in the normal range and there was mild systemic hypertension. The pulmonary hypertension may have been coincidental to the portal hypertension as opposed to being the result of it, or the patient may have had increased levels of systemic NO but decreased pulmonary microvasculature NO levels. Pulmonary hypertension may represent a collection of disease processes with diverse phenotypic expression and, therefore, differing responses to therapy.An infusion of epoprostenol has been shown as a successful therapy in reducing pulmonary hypertension before liver transplantation. [15]For how long after transplantation should the epoprostenol infusion be maintained is unknown. More severe hypertension continues to develop postoperatively in the majority of patients with severe pulmonary hypertension at the time of transplantation, and the patients die of right ventricular failure over the next 18 months. [7]Whether remodeling of pulmonary arteriolar wall hypertrophy can occur with chronic vasodilator therapy, and over what time period, is an intriguing thought. [16,17]Whether the chronic exposure of the patient to inhaled NO via nasal cannulae would be equally as effective as an infusion of epoprostenol is being explored. [18]The advantage of this technique would be the avoidance of an indwelling intravenous cannula and its associated morbidity.The role of inhaled NO and endogenous NO in endstage liver disease deserves further evaluation. Perhaps, the presence, or absence, of an elevated exhaled NO level may indicate which patients with portopulmonary hypertension will respond to exogenous inhaled NO.

S122 INTRODUCTION: The concentration of nitric oxide (NO) in exhaled breath has been demonstrated to be at increased levels in patients with severe liver cirrhosis [1]. This prospective study investigates the variation in levels of exhaled NO in patients undergoing orthotopic liver transplantation. METHOD: After IRB approval and informed consent, 8 patients with severe liver cirrhosis undergoing orthotopic liver transplantation had intraoperative levels of exhaled NO monitored. A chemiluminecence analyzer (Sievers Inc. Boulder, Co) was utilized and samples were measured from the elbow connector attaching the breathing circuit to the endotracheal tube. Nasopharyngeal produced NO was excluded from the sample by the endotracheal tube. Peak concentrations of NO were recorded during exhalation. RESULTS: See Table 1.Table 1: Peak concentrations for exhaled nitric oxide in patients during three stages of orthotopic liver transplantation.DISCUSSION: The NO measured in the exhaled breath of patients with severe liver cirrhosis may be the result of an increased production of NO by hepatocytes and Kuppfer cells in the liver, where it is then transported to the lungs as s-nitrosyl hemoglobin and released, or it may have originated from the local production of NO in the lungs [2-4]. Both of these pathways may exist together. If the liver is a significant source of this NO production, then the anhepatic phase of the transplant procedure should result in a reduction of exhaled NO levels. In this preliminary study, the trend seen in some patients corroborates this hypothesis. If this finding is confirmed by further investigation then exhaled NO analysis may provide an early indication of liver graft function.

S227 Introduction: The assessment of ventilation in the spontaneously breathing, extubated patient in the postanesthesia care unit (PACU) can be easily misinterpreted. Common observations are, respiratory rate and pattern, level of consciousness, and pulse oximetry. Despite severe hypoventilation, pulse oximetry may continue to record high oxygen saturation in patients who are receiving added O2. Respiratory rate may also correlate poorly with ventilatory depression. End-tidal carbon dioxide (ETCO (2)), which is already routinely monitored in the operating room, may be a more reliable measure of ventilatory status in extubated patients in the PACU. This prospective study evaluates the monitoring of ETCO2 in the PACU in extubated patients. Method: After IRB approval and informed consent, 17 patients who had undergone either carotid artery surgery or major orthopedic surgery were studied. These patients are routinely monitored with an intra-arterial catheter. On arrival in the PACU, ETCO2 was monitored continuously via a nasal cannula. This nasal cannula combined a sampling tube connected to an infra-red ETCO2 analyzer and an oxygen delivery tube (Salter Labs, Arvin, CA). Arterial blood gas samples were taken within 15 minutes once the patient was in the PACU and again 45 min to 1 hour later. Continuous pulse oximetry and vital signs including respiratory rate, pattern, and level of consciousness were recorded. Comparative data was analyzed using a Pearson's Correlation and a Student's t-test. Results: (Table 1)Table 1The poor correlation between ETCO2 and PaCO2 in early recovery was due to the display of multiple zero readings from the ETCO2 monitor. The corresponding pulse oximeter readings were within normal limits (> 95%); an assessment of breathing character revealed a paradoxical pattern with only intermittent nasal flow of expired air. This may be the result of residual anesthetic effects. As recovery continued, the correlation between ETCO2 and PaCO2 showed marked improvement. Conclusion: The lack of correlation between ETCO2 and PaCO2 in early recovery from general anesthesia indicates that careful observation of other clinical signs, such as respiratory pattern and level of consciousness are necessary.

S93 Introduction: Nitric oxide (NO) is used as a selective pulmonary vasodilator in adult cardiac surgery patients with acute pulmonary hypertension and right heart dysfunction. In this study we report on a two-year experience with inhaled NO in patients undergoing cardiac bypass surgery and heart transplantation. This group of patients may encounter acute increases in pulmonary artery pressures (PAP), pulmonary vascular resistance (PVR), right heart dysfunction, and alveolar-arterial gradients, especially on separating from cardiopulmonary bypass. A review of the time taken to wean off the NO was also made. Method: After FDA and IRB approval and informed consent, 24 patients met criteria to receive NO (systolic PAP >or=to 45 mm Hg, PVR > 180 dynes/s/cm5, transpulmonary gradient > 10 mm Hg, and/or right heart dysfunction). Nitric oxide was blended into the ventilatory circuit and monitored at the inspiratory limb of the Y-junction close to the endotracheal tube. Arterial blood gases were analyzed, NO and NO2 concentrations were closely monitored, and hemodynamic parameters were monitored continuously. The time taken to wean off NO was also analyzed and correlated with the duration of NO therapy. Data were analyzed using Student's t-tests and Pearson's correlations. Results: (Table 1 and Table 2)Table 1: HemodynamicsTable 2: Duration of Nitric Oxide TherapyConclusion: Nitric oxide is effective at reversing acute increases in PAP and PVR as well as improving right ventricular performance in select cardiac surgery patients. The amount of time spent on NO therapy correlated significantly with the time required to successfully wean off NO. It is of interest that over 25% of the weaning period is spent on reducing NO from 5ppm to 0ppm.

S306 Introduction: Remifentanil is a specific [micro sign]-opioid agonist which is rapidly metabolized with an ultra-short half-life (approximately 3-10 min) and no accumulation after prolonged infusion. The rapid clearance and lack of accumulation allow an infusion to be titrated to optimize postoperative pain control. The aim of this study was to compare the analgesic efficacy of intravenous remifentanil infusion and thoracic epidural infusion in patients undergoing lung transplant surgery. Methods: The charts of 13 consecutive single or bilateral sequential lung transplant patients were reviewed. The patients were divided into two groups according to the anesthetic technique. Patients in Group 1 (n = 7) received a thoracic epidural infusion of either ropivacaine 0.2% (n = 4) or a combination of bupivacaine 0.06% and fentanyl 10[micro sign]g/ml along with a light general anesthetic consisting of isoflurane. Patients in Group 2 (n = 6) received a total intravenous anesthetic technique consisting of remifentanil 0.2 to 0.4 [micro sign]g/kg/min and propofol 100-150 [micro sign]g/kg/min infusions. Muscle relaxation was achieved with vecuronium and patients were ventilated with air and oxygen combination. Patients in Group 1 continued to receive the epidural infusion, while those in Group 2 received an intravenous infusion of remifentanil for postoperative pain management. The data recorded included age, gender, weight, the anesthetic requirements, the duration of anesthesia, times to awakening (i.e., response to verbal command) and extubation, the duration of intensive care unit stay, the need for supplemental analgesics and visual analog pain scores (with 0 = no pain and 10 = severe pain). The data were analyzed using students t-test with a p value of less than 0.05 considered statistically significant. Results: The two groups were similar with respect to demographic data and the duration of anesthesia. There were no statistically significant differences between the time to extubation, visual analog pain scores and the need for supplemental analgesic medications. Although the duration of intensive care unit stay was shorter in the patients receiving thoracic epidural infusion, and the time to awakening was less in the remifentanil groups, these did not achieve statistical significance. However, the duration of analgesic infusions were significantly (p < 0.05) shorter in patients receiving remifentanil (compared to those receiving thoracic epidural). (Table 1)Table 1Conclusion: The results of this study suggests that intravenous remifentanil infusion is a satisfactory alternative to thoracic epidural analgesia. It also avoids the risks associated with epidurals, particularly, in patients requiring heparinization and cardiopulmonary bypass.

Objectives of anesthesia ventilation include maintenance of hormoxemia, normocapnia, airway climatization and minimum alveolar concentration (MAC)-based dosage of volatile anesthetic agents. If these goals are to be achieved automatically, e.g., by means of feedback control, regulated and controlled variables need to be defined. Clinically relevant controlled variables are oxygen saturation (sO(2)), end-tidal carbon dioxide concentration (etCO(2)), water content of respiratory gases, and end-tidal concentration of volatile anesthetic agents (etVA). Corresponding regulated variables include inspiratory oxygen concentration (FIO2), water content of inspiratory gas (FIH2O), inspiratory concentration of volatile anesthetic agents and - for all variables - ventilatory minute volume. In particular if gases other than oxygen are used, e.g., N2O or N-2, the system volume also needs to be controlled. Obviously, the fresh gas flow (FGF) rate is neither a controlled nor a regulated variable for any of the qualities pertinent to anesthesia ventilation; rather the contrary, FGF adds noise to the system and any change of FGF adversely affects equilibria of minute ventilation, FIO2, and volatile agent concentration. However, most conventional anesthesia workstations (per ISO 5358 or EN 740) allow user-adjustable FGF, adding a source of error to all control systems. We have designed an anesthetic workstation, complying with EN 740, which has eliminated FGF as an independent variable and which allows closed-loop feedback control of relevant variables. It is a closed system without valves, offering further advantages with respect to work of breathing, airway climatization, cost, environmental protection, and quantitative anesthesia. The PhysioFlex is a computer-controlled high-flaw closed-circuit workstation, relying on three hierarchically arranged levels of feedback control: oxygen, volume, and agent. Controlled variables are FIO2, system volume and etVA, corresponding regulated variables are the volumes of oxygen, N2O/N-2, and liquid VA, digitally fed into the system. All variables are adjusted automatically (with reference to the computer's physiology and pharmacokinetics databank) to the respective set-point selected by the user. Integration of an activated charcoal filter allows reduction of VA concentration without opening the system. High flow within the system provides lag-free equilibrium of all concentrations, allowing feedback control without oscillation. A backup safety system protects against wrong dosage resulting from erroneous measurements (single fault condition). The digital administration of oxygen allows online monitoring of oxygen uptake, reflecting the patients (V) over dot O-2 (oxygen uptake). Everyone has learnt to trust feedback control systems in daily life and sometimes considers them superior to manual control, e.g., the autopilot in aviation. Applying the same philosophy to anesthesia ventilation relieves the clinician from some needless and distracting routines, giving him more time to take care of his patient.

S228 Introduction: A thrombelastogram (TEG) may take 10-15 minutes before an initial evaluation can be made. A complete analysis including clot lysis may take 30 - 60 min. The presence of trace amounts of heparin may prolong the R-time such that no trace develops at all. In an attempt to accelerate the development of the TEG, the addition of recombinant human tissue factor (RHTF) and heparinase to aliquots of blood were prospectively studied. Methods: After IRB approval, 25 patients undergoing liver transplantation were prospectively studied. Blood samples were analyzed at various intervals during the surgery. A control TEG was set up at the same time as a second sample with the addition of 0.01 ml RHTF. At the reperfusion stage, a period when a heparin effect is frequently encountered a third sample was run with the addition of heparinase and a fourth sample with RHTF and heparinase. Clot lysis index was calculated by the formula MA60/MA x 100. Statistical analysis was completed using Paired Students t-tests and Pearson's correlation. Results: (Table 1)Table 1Heparinase only significantly reduces R-time when heparin effect is present (R-time = [infinity] and TEG shows a straight line). Discussion: The addition of RHTF reduced R-time allowing a more rapid analysis of the TEG. However, the MA was augmented in those TEGs enhancing the quality of clot formation. Clot lysis was detected earlier. The addition of heparinase at reperfusion reduced R-time but not as rapidly as the RHTF sample, but it also enhanced the clot formation as measured by MA. Conclusion: RHTF added to the TEG sample accelerates the diagnosis of clot lysis, that may be helpful in the administration of anti-fibrinolytic agents. However, the quality of the TEG is enhanced. Heparinase is effective at removing a heparin effect on the TEG, allowing a more rapid diagnosis of lysis in these patients. It is of interest that the MA was also increased by heparinase.

S217 Introduction: Inhaled nitric oxide (NO) is being used more frequently in clinical practice. The transport of patients who are dependent on NO may present a technical challenge. The I-NOvent[registered sign] (Ohmeda, Inc., Madison, WI) delivery system has recently become available. It is designed to deliver precise levels of NO, up to 40 ppm, when connected to a mechanical ventilator. During manual ventilation for transport the maximum level delivered is 10 ppm. As many patients may require more than 10 ppm we have designed a transport system utilizing the I-NOvent[registered sign] that can deliver up to 40 ppm. Method: A manual transport system was constructed of a self-inflating resuscitation bag, a ported 22 mm female/male adapter, a one-way valve, and a disposable breathing circuit (Airlife Universal Manifold and Nebulizer, Baxter Healthcare Corp., Santa Ana, CA). The I-NOvent was attached to this assembly. The injector module connected to the ported adapter and the sensor attached between the flex tubing and the exhalation valve (Figure 1). This assembly was connected to a test lung and concentrations of NO from 15 to 40 ppm were delivered to the system at three different rates of manual ventilation. The actual concentrations of NO delivered to the test lung were measured. Two different lengths of flex tubing were also tested. Data were analyzed using a Pearson's correlation.Figure 1Results: The length of flex tubing of 6 inches to 24 inches did not alter the concentration of NO delivered. (Table 1)Table 1: Measured NO at different settings and breaths per minute (BPM).Conclusion: The designed transport system delivers accurate concentrations of NO up to 40 ppm at respiratory rates of 12-20 bpm.

Patients undergoing total hip arthroplasty (THA) may rarely develop neurological complications that may present as transient confusion or, if severe, as coma or death [1]. Suggested etiologies for these impairments include hypoxia caused by pulmonary embolism or from paradoxical cerebral emboli passing through a patent foramen ovale or other intracardiac shunt [2,3]. The pathogenesis of neurological problems surrounding arthroplastic surgery is thought to be fat emboli from the bone marrow being released by an increase in intramedullary pressure [2,4]. We report two cases in which patients underwent successful and uncomplicated THA but developed critical neurologic impairment hours later, leading to the death of one patient and the prolonged recovery of the other. The symptoms of this neurological complication were atypical in that they did not present until 2-3 h after what seemed to be a normal recovery from anesthesia and surgery. Neither patient, on close examination, had demonstrable intracardiac shunts. Case Reports Case 1 A 73-yr-old, 100-kg man underwent a revision of a left hip hemiarthroplasty after loosening had occurred in the original arthroplasty. General anesthesia was induced with midazolam 3 mg, propofol 100 mg, and rocuronium 10 mg IV; maintained with desflurane 3%-5% in a 50% air/oxygen mixture; and supplemented with an intrathecal hypertonic solution of tetracaine 12 mg and morphine 0.2 mg. Monitoring devices included continuous pulse oximetry, capnography, electrocardiogram, esophageal thermometer, and a left radial artery catheter. Revision of the left hip hemiarthroplasty was performed using the anterolateral approach. The femoral canal and the acetabulum were reamed to accept larger components, and a medial defect in the proximal femur was supported by an allograft wired into place. No intraoperative complications were encountered with anesthesia or surgery, and after tracheal extubation, the patient was taken to the postanesthesia care unit awake and in stable condition. Surgery time was 90 min. Blood loss was estimated to be 400 mL, and 2500 mL of crystalloid fluid was infused. Postoperative antithrombotic prophylaxis was instituted with low-molecular-weight heparin therapy. Over the course of 2.5 h, the patient progressively developed impairment in his level of consciousness, to the point where he became unresponsive despite stable hemodynamic variables. The oxygen saturation level remained at 99%, and endotracheal intubation was performed. A cranial computer tomography scan showed no acute lesions. His neurologic status did not improve, and a magnetic resonance imaging (MRI) scan of the brain performed the following day was reported to be normal. A repeat MRI scan on the 12th day postsurgery showed multiple lesions in the white matter and in the right middle cerebellar peduncle and left thalamus consistent with small vessel occlusion. Supportive care was withdrawn, and the patient died the next day. An autopsy of the brain showed multiple disseminated lesions consistent with microembolic infarcts. The examination of the heart did not reveal any intracardiac shunts. Case 2 A 37-yr-old, 67-kg woman underwent bilateral THA for avascular necrosis of the hip joints. Her medical history was noteworthy for cardiomyopathy treated by orthotopic heart transplantation 2 yr earlier. A preoperative transesophageal echocardiogram revealed no abnormalities. General anesthesia was induced with midazolam 3 mg, fentanyl 150 [micro sign]g, and etomidate 15 mg and maintained with isoflurane 0.5%-1% in a 50% air/oxygen mixture. Epidural bupivacaine 0.25% was continuously infused. Monitoring devices included continuous pulse oximetry, capnography, electrocardiogram, esophageal thermometer, and left radial artery and pulmonary artery catheters. Bilateral THA was performed sequentially on the right and left joints using a lateral decubitus position. Cementless hip arthroplasty was performed. The femoral prostheses required considerable reaming. The wounds were irrigated copiously and then closed. No intraoperative complications were encountered. The patient was taken to the intensive care unit awake and responsive. Surgery time was 160 min, and blood loss was estimated to be 800 mL with 300 mL of washed, salvaged blood returned intraoperatively, together with 3000 mL of crystalloid fluid. Postoperative antithrombotic prophylaxis was instituted with low-molecular-weight heparin therapy. Over the course of the first 3 h postoperatively, the patient developed a progressive impairment in the level of consciousness and became unresponsive to stimuli. Endotracheal intubation was performed, and the patient was mechanically ventilated. Over the course of a few hours, she developed a right gaze and produced pink bronchial secretions, and her pulmonary artery pressure increased to 60/24 mm Hg. She developed an acute respiratory distress syndrome. A computer tomography scan on the first day postsurgery showed no acute lesions. A MRI scan demonstrated diffuse small lesions in the brain and kidney consistent with fat emboli. Her recovery was slow, but the encephalopathy gradually resolved, and she fully recovered 4 mo postoperatively. Discussion Both patients seem to have suffered from direct embolization to the brain with subsequent occlusion of the microvasculature and development of encephalopathic changes. There was no clinical or postmortem evidence of any source of embolism other than fat embolism. Both patients remained in sinus rhythm, and neither patient had evidence of intracardiac shunts, as demonstrated by either a postmortem examination of the heart or an echocardiographic examination. Transpulmonary passage of marrow fat dislodged in the course of intramedullary surgery or the formation of fat emboli in the systemic circulation seems to be the most likely explanation for these events. Transpulmonary systemic fat embolism has been demonstrated in mongrel dogs [5], and the transpulmonary passage of air emboli has been speculated to occur in humans [6,7]. Fat globules originating from bone marrow are capable of transforming and reducing their size under increasing pressure, and they were found in the brains on autopsy. None of the dogs had an intracardiac shunt on autopsy. Fat emboli may also be derived from chylomicrons agglutinated in the blood [8]. The first patient we reported underwent a revision of a hip hemiarthroplasty and should not have had significant amounts of embolic material released. The MRI scan and autopsy, however, both support a diagnosis of embolic brain insult. In this patient, plasma-derived fat embolism could be the cause for the neurological deficit. The second patient had bilateral THA; therefore, potentially significant amounts of embolic material entered the circulation. The clinical findings and imaging studies support a diagnosis of fat embolism syndrome. The primary event leading to the neurologic injury may have been transpulmonary passage of microembolic material and subsequent lodging in the capillaries of the cerebrum. The unusual presentation in both patients is that, initially, they seemed neurologically intact and only developed symptoms over several hours postoperatively. This may be the result of the gradual development of cerebral edema after embolization, or it may have been caused by the gradual release of free-fatty acids and glycerin from the fat cells and the resulting toxic effect on the brain cells. No other clinical evidence of fat emboli, or of any other source of emboli, were detected at the time of the neurological insult. The ultimate recovery of the second patient without residual neurological deficit suggests that if a patient can survive the initial insult, the brain can fully recover. However, to detect the cerebral insult early, patients undergoing major joint arthroplasty should remain under close observation for several hours postoperatively. If the patient is transferred to the general nursing unit, routine frequent monitoring should include a sedation assessment so that deterioration in mental function can be detected early and supportive care instituted [9]. The immediate detection of mental deterioration and the aggressive use of supportive care to reduce the extent of brain injury can result in a good outcome. Serial brain scans may be necessary to demonstrate pathology. The presence of intracardiac shunts is not essential for paradoxical embolization to take place.