A comparison of sirolimus vs. calcineurin inhibitor-based immunosuppressive therapies in liver transplantation.

BACKGROUND: Sirolimus is a potent immunosuppressive agent whose role in liver transplantation has not been well-described. AIM: To evaluate the efficacy and side-effects of sirolimus-based immunosuppression in liver transplant patients. METHODS: Retrospective analysis of 185 patients who underwent orthotopic liver transplantation. Patients were divided into three groups: group SA, sirolimus alone (n = 28); group SC, sirolimus with calcineurin inhibitors (n =56) and group CNI, calcineurin inhibitors without sirolimus (n = 101). RESULTS: One-year patient and graft survival rates were 86.5% and 82.1% in group SA, 94.6% and 92.9% in group SC, and 83.2% and 75.2% in group CNI (P = N.S.). The rates of acute cellular rejection at 12 months were comparable among the three groups. At the time of transplantation, serum creatinine levels were significantly higher in group SA, but mean creatinine among the three groups at 1 month was similar. More patients in group SA required dialysis before orthotopic liver transplantation (group SA, 25%; group SC, 9%; group CNI, 5%; P = 0.008), but at 1 year, post-orthotopic liver transplantation dialysis rates were similar. CONCLUSIONS: Sirolimus given alone or in conjunction with calcineurin inhibitors appears to be an effective primary immunosuppressant regimen for orthotopic liver transplantation patients. Further studies to evaluate the efficacy and side-effect profile of sirolimus in liver transplant patients are warranted.

Outcome prediction of emergency patients by noninvasive hemodynamic monitoring.

OBJECTIVES: We used noninvasive hemodynamic monitoring in the initial resuscitation beginning in the emergency department (ED) for the following reasons: (1) to describe early survivor and nonsurvivor patterns of emergency patients in terms of cardiac, pulmonary, and tissue perfusion deficiencies; (2) to measure quantitatively the net cumulative amount of deficit or excess of the monitored functions that correlate with survival or death; and (3) to explore the use of discriminant analysis to predict outcome and evaluate the biological significance of monitored deficits. METHODS: This is a descriptive study of the feasibility of noninvasive monitoring of patients with acute emergency conditions in the ED to evaluate and quantify hemodynamic deficits as early as possible. The noninvasive monitoring systems consisted of a bioimpedance method for estimating cardiac output together with pulse oximetry to reflect pulmonary function, transcutaneous oxygen tension to reflect tissue perfusion, and BP to reflect the overall circulatory status. These continuously monitored noninvasive measurements were used to prospectively evaluate circulatory patterns in 151 consecutively monitored severely injured patients beginning with admission to the ED in a university-run county hospital. The net cumulative deficit or excess of each monitored parameter was calculated as the cumulative difference from the normal value vs the time-integrated monitored curve for each patient. The deficits of cardiac, pulmonary, and tissue perfusion functions were analyzed in relation to outcome by discriminant analysis and were cross-validated. RESULTS: The mean (+/- SEM) net cumulative excesses (+) or deficits (-) from normal in surviving vs nonsurviving patients, respectively, were as follows: cardiac index (CI), +81 +/- 52 vs -232 +/- 138 L/m(2) (p = 0.037); arterial hemoglobin saturation, -1 +/- 0.3 vs -8 +/- 2.6%/h (p = 0.006); and tissue perfusion, +313 +/- 88 vs -793 +/- 175, mm Hg/h (p = 0.001). The cumulative mean arterial BP deficit for survivors was -10 +/- 13 mm Hg/h, and for nonsurvivors it was -57 +/- 24 mm Hg/h (p = 0.078). CONCLUSIONS: Noninvasive monitoring systems provided continuously monitored on-line displays of data in the early postadmission period from the ED to the operating room and to the ICU for early recognition of circulatory dysfunction in short-term emergency conditions. Survival was predicted by discriminant analysis models based on the quantitative assessment of the net cumulative deficits of CI, arterial hypoxemia, and tissue perfusion, which were significantly greater in the nonsurvivors.

Maternal and infant complications in high and normal weight infants by method of delivery.

OBJECTIVE: To estimate the population risks of maternal and infant complications with the birth of macrosomic (at least 4000 g) compared with normal weight infants. METHODS: Term, singleton infants were identified from the state of Washington's birth event records database for 1990. Diagnosis codes from the Internal Classification of Diseases (9th revision) were used to identify delivery method and previously defined complications. We adjusted for maternal demographic and clinical factors using multivariable logistic regression to derive the risk of each maternal and infant complication. RESULTS: The incidence of macrosomia was 13% (8815 of 66,086). Vaginal birth of macrosomic infants was associated with low incidence of complications except for shoulder dystocia (11%) and postpartum hemorrhage (5%). Postpartum infection was the most common complication for women who had cesarean delivery after labor (5%), and complications for women who had cesarean without labor were rare (less than 3%). Neonatal complications were rare. Among infants with shoulder dystocia, the risks of asphyxia (adjusted relative risk [RR] 1.2, 95% confidence interval [CI] 0.6, 2.3), birth trauma (RR 0.6, 95% CI 0.2, 1.6), long-bone injury (RR 1.2, 95% CI 0.6, 2.4), seizures (RR 1.0, 95% CI 0.0, 25.0), and facial palsy (RR 2.2, 95% CI 0.2, 44.4) were not significantly different for macrosomic and normal weight infants; however, macrosomic infants had a significantly increased risk of Erb palsy (RR 3.5, 95% CI 1.8, 7.5). CONCLUSION: This population-based study showed that most macrosomic infants are delivered vaginally with low rates of maternal and neonatal complications. Macrosomic infants have higher rates of Erb palsy, but similar rates of other serious complications of shoulder dystocia when compared with normal weight infants.

Abdominal computed tomography for the diagnosis of intra-abdominal sepsis in critically injured patients: fishing in murky waters.

HYPOTHESIS: Abdominal computed tomographic (ACT) scans are useful in the evaluation of sepsis of unknown origin in patients with major trauma. DESIGN: Prospective case series of consecutive patients. SETTING: Intensive care unit of level I academic trauma center. PATIENTS: Eighty-five critically injured patients admitted to the intensive care unit in 32 months (6% of all intensive care unit admissions) who developed sepsis of unknown origin. INTERVENTIONS: One hundred sixty-one ACT scans. MAIN OUTCOME MEASURES: Sensitivity and specificity of the ACT scans, number of patients subjected to changes in treatment following an ACT scan. RESULTS: Forty-nine patients (58%) had an intraabdominal focus of infection identified on ACT scan. Penetrating trauma and emergent laparotomy were the only independent factors associated with abnormal findings on ACT scan. The sensitivity and specificity of the test were 97.5% and 61.5%, respectively. Overall, 59 patients (69%) benefited from treatment changes after an ACT scan. CONCLUSION: Abdominal computed tomographic scans reliably identify intra-abdominal foci of infection in patients with major trauma evaluated for sepsis of unknown origin.

Timing of fracture fixation in blunt trauma patients with severe head injuries.

BACKGROUND: Early fracture fixation in blunt trauma patients is suggested to decrease postoperative morbidity by allowing early mobilization and reducing the release of harmful inflammatory mediators. Some studies have challenged this concept in the presence of severe associated injuries, and especially head trauma. METHODS: The records of 47 consecutive blunt trauma patients with severe head injuries, as defined by a Glasgow Coma Score (GCS) < or =8 and a head Abbreviated Injury Score (AIS) > or =3, and long bone fractures requiring surgical fixation were reviewed. The study population was divided into the early fixation (EF) group, consisting of 22 patients who underwent fracture fixation within 24 hours of admission (mean time 17 +/- 8.5 hours); and the late fixation (LF) group, consisting of 25 patients, who had orthopedic repair at a later time (mean 143 +/- 178 hours). RESULTS: The two groups were similar in terms of overall injury severity, neurologic injuries, hemodynamic and neurologic status on admission, and operations received. Patients in the EF group had a higher injury severity of extremity fractures (extremity AIS: 2.9 +/- 0.2 versus 2.4 +/- 0.5, P = 0.0002) and a higher incidence of open fractures (72% versus 36%, P = 0.02). There was no difference in intraoperative and postoperative hypoxic and hypotensive episodes. Neurologic, orthopedic, and general complications were the same between the two groups. The mean GCS on discharge was 12 +/- 3 for both groups with equal distribution among patients. Although there was a trend toward longer hospital stay (25 +/- 17 versus 17 +/- 10 days, P = 0.057) among LF patients, mechanical ventilation days, length of stay, and mortality were not different. CONCLUSIONS: Timing of fracture fixation in this group of blunt trauma patients with severe head injuries did not influence morbidity, mortality, or neurologic outcome.

Reliable variables in the exsanguinated patient which indicate damage control and predict outcome.

BACKGROUND: Exsanguination as a syndrome is ill defined. The objectives of this study were to investigate the relationship between survival and patient characteristics--vital signs, factors relating to injury and treatment; determine if threshold levels of pH, temperature, and highest estimated blood loss can predict survival; and identify predictive factors for survival and to initiate damage control. MATERIAL AND METHODS: A retrospective 6-year study was conducted, 1993 to 1998. In all, 548 patients met one or more criteria: (1) estimated blood loss > or =2,000 mL during trauma operation; (2) required > or =1,500 mL packed red blood cells (PRBC) during resuscitation; or (3) diagnosis of exsanguination. Analysis was made in two phases: (1) death versus survival in emergency department (ED); (2) death versus survival in operating room (OR). Statistical methods were Fisher's exact test, Student's t test, and logistic regression. RESULTS: For 548 patients, mean Revised Trauma Score 4.38, mean Injury Severity Score 32. Penetrating injuries 82% versus blunt injuries 18%. Vital statistics in emergency department: mean blood pressure 63 mm Hg, heart rate 78 beats per minute. Mean OR pH 7.15 and temperature 34.3 degrees C. Mortality was 379 of 548 (69%). Predictive factors for mortality (means): pH < or =7.2, temperature <34 degrees C, OR blood replacement >4,000 mL, total OR fluid replacement >10,000 mL, estimated blood loss >15 mL/minute (P <0.001). Analysis 1: death versus survival in ED, logistic regression. Independent risk factors for survival: penetrating trauma, spontaneous ventilation, and no ED thoracotomy (P <0.001; probability of survival 0.99613). Analysis 2: death versus survival in OR, logistic regression. Independent risk factors for survival: ISS < or =20, spontaneous ventilation in ED, OR PRBC replacement <4,000 mL, no ED or OR thoracotomy, absence of abdominal vascular injury (P <0.001, max R(2) 0.55, concordance 89%). CONCLUSIONS: Survival rates can be predicted in exsanguinating patients. "Damage control" should be performed using these criteria. Knowledge of these patterns can be valuable in treatment selection.

A randomized trial of nasopharyngeal-synchronized intermittent mandatory ventilation versus nasopharyngeal continuous positive airway pressure in very low birth weight infants after extubation.

OBJECTIVE: To prospectively compare the incidence of respiratory failure in premature infants randomized to receive either nasopharyngeal continuous positive airway pressure (NPCPAP) or nasopharyngeal-synchronized intermittent mandatory ventilation (NP-SIMV) in the immediate postextubation period. STUDY DESIGN: This is a prospective study of very low birth weight (VLBW) infants randomized at the time of extubation to receive either NPCPAP or NP-SIMV in a university-based level III neonatal intensive care unit. Statistical analysis were performed with the Mann-Whitney U test for continuous and ordinal variables, and with the chi-squared test or Fisher's exact test for categorical variables. RESULTS: A total of 41 VLBW infants were studied; 19 were in the NPCPAP group, and 22 were in the NP-SIMV group. Respiratory failure after extubation in the NP-SIMV group was significantly lower that in the NPCPAP group (5% vs 37%, respectively (p = 0.016). No statistically significant differences between groups with regard to demographics, severity of initial illness and associated complications, time to extubation, ventilatory management before extubation, weight, age, or nutritional status at the time of extubation were noted.

[Prognosis of severe trauma outcome using noninvasive monitoring]. / Predskazanie iskhoda tiazheloi travmy s pomoshch'iu neinvazivnogo monitoringa.

The purpose of the case study was, firstly, to evaluate (starting from the time the patients are admitted to the intensive care unit--ICU) a type of cardiac, pulmonary and peripheral microcirculation in patients with severe traumas by using a multi-component and invasion-free monitoring; the second purpose was to measure quantitatively the changes in the cardiac, pulmonary and peripheral hemodynamics leading to recovery or death; and finally, it was to investigate the effectiveness of applying the discriminative analysis for the sake of assessing the biological value of the controllable changes and of forecast outcome. The invasion-free monitoring system comprising the below tools was in use: an improved bio-impedance method (evaluation of the cardiac output), pulsometry (examination of the pulmonary function), transcutaneous oxygen pressure (tissue perfusion function) and arterial blood pressure (ABP--general circulation status). The results of continuously controllable invasion-free measurements were used for a prospective evaluation at the emergency unit of the county hospital, which was supervised by the university. The accumulated integral values of the deficit or excess of each controllable parameter were calculated by using the differences between the normal values and the values obtained for each patient and for the groups of survivors and dead. A probable outcome and a degree of the deficit of the pulmonary and cardiac functions as well as of the tissue-perfusion function were analyzed by using the discriminant function. The values of pure aggregate deficits (-) or excesses (+) were for the survivors and dead, respectively, as follows: cardiac index--(+)93 +/- 49.8 l/m2 versus -232 +/- 138 l/m2 (p < 0.07); mean ABD(-)-12 +/- 12.4 mm Hg versus -57 +/- 23.5 mm Hg (p < 0.066); arterial saturation(-)-1 +/- 0.09% h versus -9 +/- 2.6% h (p < 0.001): and tissue perfusion--(+)311 +/- 87 tor/h versus 793 +/- 175 tor/h (p < 0.0001). The pure aggregate value of reduced circulation, tissue perfusion and of hypoxemia degree was found to be higher in the dead versus the survivors. The invasion-free monitoring systems secure a constant real-time control over the data, which makes the circulatory malfunction revealed as soon as possible in emergency settings. The mentioned systems can be used to describe, for each patients, a temporal hemodynamic model and to evaluate quantitatively a functional-deficit severity; they also provide for composing a clear-cut and successive treatment scheme from the emergency stage to the intensive care unit.

Time course of the intrahepatic lesion of extrahepatic biliary atresia: a morphometric study.

The time course of the intrahepatic lesions of untreated extrahepatic biliary atresia was evaluated by morphometric analysis of 49 specimens from 27 patients. The data show an early phase of rapid bile ductular proliferation, with peak in this material at 205 days, followed by rapid duct regression to approximately 400 days, and slower progressive intrahepatic duct loss thereafter. The ratio of ducts to connective tissue in portal tracts follows a similar course. Connective tissue in portal tracts rises on a slower course and continues to increase after maximum duct regression is reached, so the ratio of parenchyma to fibrous septa falls over the later course of the process. Although duct and connective tissue proliferation in hepatic portal tracts is associated in many liver diseases, the data of this study demonstrate dissociability of the relationships, with the fibrosis in the later stages of the intrahepatic process in extrahepatic biliary atresia apparently neither responsive to nor inducing biliary ductular proliferation.

Cesarean deliveries for medicaid patients: a comparison in public and private hospitals in Los Angeles county.

OBJECTIVE: The aims of the study were to describe the difference in cesarean delivery rates for Medicaid patients according to hospital type and adjusted for case mix and to determine cost implications for additional cesarean deliveries. STUDY DESIGN: This retrospective study used California discharge data for 92,800 patients delivered in 78 hospitals in Los Angeles County during 1991. Multivariable logistic regression was used to adjust for case mix and to calculate adjusted cesarean delivery rates according to hospital type. Cost estimates assumed $821 per day hospital reimbursement. RESULTS: The unadjusted cesarean delivery rate in private nonteaching hospitals (reference group) was 24.5%, compared with 13.2%, 17.4%, and 16.5% in public, health maintenance organization, and private teaching hospitals, respectively. Adjustment for case mix decreased the cesarean delivery rate in public (9.0%), health maintenance organization (12.0%), and private teaching hospitals (8.0%). Cesarean deliveries performed on patients in private nonteaching hospitals result in an additional $13.6 million in Medicaid health care expenses. CONCLUSIONS: There are increased health care costs related to increased cesarean deliveries performed on Medicaid patients in private nonteaching hospitals.

Preferentially longer survival of males than of females with untreated extrahepatic biliary atresia: correlations with time course of intrahepatic lesions and suggestion of possible ethnic influences.

Males with untreated or unsuccessfully treated extrahepatic biliary atresia show statistically significantly longer survival than females. Females show a greater degree of intrahepatic biliary ductular proliferation than males in the early phase of the process (to age approximately 200 days) and greater duct regression and more rapid connective tissue proliferation than males from approximately 200 to 400 days. Females also show greater frequency of statistically significant hepatomegaly than males over the first year. The black and Hispanic patients in this series tended to show a less marked degree of bile ductule proliferation in the early phase of the process than other patients, but the numbers of such patients available for study were not enough for statistical significance. This point, and its possible clinical correlates, will require further analysis, as will possible biochemical explanations for the differences between males and females in the time course of the intrahepatic lesions of extrahepatic biliary atresia.

Relative bradycardia in patients with traumatic hypotension.

BACKGROUND: Tachycardia is considered a physiologic response to traumatic hypotension. The inability of the heart to respond to shock with tachycardia has been described as paradoxical bradycardia or relative bradycardia. The incidence and clinical significance of this condition in major trauma is not known. The objective of this study was to examine the incidence and prognostic significance of tachycardia and relative bradycardia in patients with traumatic hypotension. Relative bradycardia is defined as a systolic pressure < or = 90 mm Hg and a pulse rate < or = 90 beats per minute. METHODS: This is a retrospective study conducted at a large Level I academic trauma center during a 4-year period. Seventeen demographic and injury severity factors were analyzed for their possible role in tachycardic or bradycardic response in hypotensive patients. Incidence and mortality were derived for each subpopulation. Bivariate analysis of the association of incidence and mortality with each risk factor was performed. Factors with p values < 0.2 were included in stepwise logistic regression analyses that identified significant risk factors and derived adjusted relative mortality risks between tachycardic and bradycardic hypotensive patients. RESULTS: Excluding transfers and patients dead on arrival, 10,833 major trauma patients were seen during the study period. Seven hundred fifty patients (6.9%) had systolic blood pressure < or = 90 mm Hg; 533 patients had tachycardia (overall incidence of 4.9%, or 71.1% of hypotensive patients), and 217 patients had bradycardia (overall incidence of 2.0%, or 28.9% of hypotensive patients). The overall crude mortality was 29.2% among tachycardia patients and 21.7% among bradycardia patients (crude relative risk = 1.34; 95% confidence interval = 1.00-1.81; p = 0.047). The adjusted relative mortality risk between the two groups was 1.23 (95% confidence interval = 0.84-1.73; p = 0.284). Multivariate analysis showed that patients with relative bradycardia in the subgroups with Injury Severity Scores > or = 16, chest Abbreviated Injury Scale scores > or = 3, or abdominal Abbreviated Injury Scale scores > or = 3 had significantly better survival than patients with similar injuries presenting with tachycardia. CONCLUSION: Relative bradycardia in hypotensive trauma patients is a common hemodynamic finding. Mortality among tachycardic patients was more predictable than among bradycardic patients using commonly used demographic and injury indicators. The presence of relative bradycardia in some subgroups of patients with severe injuries seems to be associated with better prognosis than the presence of tachycardia.