Influence of anthropometric features on graft diameter in ACL reconstruction.

BACKGROUND: There is a paucity of literature regarding the influence of anthropometric features on the hamstring graft obtained in ACL reconstruction. This study was undertaken to assess the influence of anthropometric measurements on the graft diameter obtained at ACL reconstruction surgery within the European population. We hypothesise that anthropometric features do influence graft thickness in ACL reconstruction. MATERIALS AND METHODS: Data from 121 consecutive patients who had undergone ACL reconstruction by the same surgeon using quadruple hamstring grafts were analysed. The body mass index (BMI), height and weight of these patients were correlated with the graft diameter obtained during surgery. Regression analysis was undertaken to assess the influence of individual anthropometric variables on the graft diameter. RESULTS: There were 121 patients with mean age of 32 years (14-55). There was a statistically significant positive correlation individually between the height and graft diameter (r = 0.38, p < 0.01) as well as between the body weight and graft diameter (r = 0.29, p < 0.01). However, when the body mass index was calculated, the correlation was not statistically significant (r = 0.08, p > 0.1). Regression analysis confirmed that BMI was not statistically significant as a predictor of hamstring graft diameter whereas height was statistically the most important predictor (F = 20.1; p < 0.01).This yielded the predictive equation, graft diameter = 4.5 + 0.02 x Ht (in cm). CONCLUSION: Although body mass index did not significantly correlate, body height may be a predictive variable in predicting the graft diameter in ACL reconstruction and provide useful pre operative information.

Kidney allocation to liver transplant candidates with renal failure of undetermined etiology: role of percutaneous renal biopsy.

The feasibility, value and risk of percutaneous renal biopsy (PRB) in liver transplant candidates with renal failure are unknown. PRB was performed on 44 liver transplant candidates with renal failure of undetermined etiology and glomerular filtration rate (GFR) <40 mL/min/1.73 m(2) (n = 37) or on renal replacement therapy (RRT) (n = 7). Patients with >or=30% interstitial fibrosis (IF), >or=40% global glomerulosclerosis (gGS) and/or diffuse glomerulonephritis were approved for simultaneous-liver-kidney (SLK) transplantation. Prebiopsy GFR, urinary sodium indices, dependency on RRT and kidney size were comparable between 27 liver-transplant-alone (LTA) and 17 SLK candidates and did not relate to the biopsy diagnosis. The interobserver agreement for the degree of IF or gGS was moderate-to-excellent. After a mean of 78 +/- 67 days, 16 and 8 patients received LTA and SLK transplants. All five LTA recipients on RRT recovered kidney function after transplantation and serum creatinine was comparable between LTA and SLK recipients at last follow-up. Biopsy complications developed in 13, of these, five required intervention. PRB is feasible in liver transplant candidates with renal failure and provides reproducible histological information that does not relate to the pretransplant clinical data. Randomized studies are needed to determine if PRB can direct kidney allocation in this challenging group of liver transplant candidates.

Acute myopathy after liver transplantation.

Acute myopathy is a cause of weakness and additional morbidity in a variety of critically ill patients, including transplant recipients. We report the incidence of and risk factors associated with acute myopathy after orthotopic liver transplantation (OLTx). One hundred consecutive adult patients were prospectively assessed for muscle weakness after OLTx. Electrodiagnostic studies and muscle biopsies were performed on consenting affected patients. Potential risk factors for myopathy were evaluated in patients with myopathy versus control subjects. Seven patients developed acute persistent weakness after OLTx. Electrodiagnostic studies were consistent with a necrotizing myopathy. Histopathologic evaluation in five revealed a necrotizing myopathy with loss of myosin thick filaments. A higher initial index of illness severity, dialysis requirement, and higher doses of glucocorticoids were associated with development of myopathy. Patients with myopathy subsequently remained in the intensive care unit (ICU) longer than unaffected patients. In conclusion, acute substantial weakness was a source of additional morbidity in 7% of patients after OLTx. Most had myopathy with loss of myosin thick filaments. Patients with greater severity of illnesses and renal failure requiring dialysis were more likely to be affected. The effect of reducing exposure to corticosteroids in high-risk patients warrants further investigation.

Clinical and laboratory evaluation of the safety of a bioartificial liver assist device for potential transmission of porcine endogenous retrovirus.

BACKGROUND: The potential risk of transmission of porcine endogenous retroviruses (PERV) from xenogeneic donors into humans has been widely debated. Because we were involved in a phase I/II clinical trial using a bioartificial liver support system (BLSS), we proceeded to evaluate the biosafety of this device. MATERIALS AND METHODS: The system being evaluated contains primary porcine hepatocytes freshly isolated from pathogen-free, purpose-raised herd. Isolated hepatocytes were installed in the shell, which is separated by a semipermeable membrane (100-kD nominal cutoff) from the lumen through which the patients' whole blood is circulated. Both before and at defined intervals posthemoperfusion, patients' blood was obtained for screening. Additionally, effluent collected from a clinical bioreactor was analyzed. The presence of viral particles was estimated by reverse transcriptase-polymerase chain reaction (RT-PCR) and RT assays. For the detection of pig genomic and mitochondrial DNA, sequence-specific PCR (SS-PCR) was used. Finally, the presence of infectious viral particles in the samples was ascertained by exposure to the PERV-susceptible human cell line HEK-293. RESULTS: PERV transcripts, RT activity, and infectious PERV particles were not detected in the luminal effluent of a bioreactor. Culture supernatant from untreated control or mitogen-treated porcine hepatocytes (cleared of cellular debris) also failed to infect HEK-293 cell lines. Finally, RT-PCR, SS-PCR, and PERV-specific RT assay detected no PERV infection in the blood samples obtained from five study patients both before and at various times post-hemoperfusion. CONCLUSION: Although longer patient follow-up is required and mandated to unequivocally establish the biosafety of this device and related bioartificial organ systems, these analyses support the conclusion that when used under standard operational conditions, the BLSS is safe.

Etiology of metabolic acidosis during saline resuscitation in endotoxemia.

We sought to understand the mechanism of metabolic acidosis that results in acute resuscitated endotoxic shock. In six pentobarbital-anesthetized dogs, shock was induced by Escherichia coli endotoxin infusion (1 mg/kg) and was treated with saline infusion to maintain mean arterial pressure > 80 mmHg. Blood gases and strong ions were measured during control conditions and at 15, 45, 90, and 180 min after endotoxin infusion. The mean saline requirement was 1833+/-523 mL over a 3 h period. The total acid load from each source was calculated using the standard base deficit. The mean arterial pH decreased from 7.32 to 7.11 (p < .01); pCO2 and lactate were unchanged. Saline accounted for 42% of the total acid load. However, 52% of the total acid load was unexplained. Although serum Na+ did not change, serum Cl-increased (127.7+/-5.1 mmol/L vs. 137.0+/-6.1 mmol/L; p=.016). We conclude that saline resuscitation alone accounts for more than one-third of the acidosis seen in this canine model of acute endotoxemia, whereas lactate accounts for less than 10%. A large amount of the acid load can be attributed to differential Na+ and Cl- shifts from extravascular to vascular spaces.

Release of lactate by the lung in acute lung injury.

UNLABELLED: The pathogenesis of hyperlactatemia during sepsis is poorly understood. We have previously described an increase in lactate concentration across the lung in the dog during early endotoxemia. Accordingly, we sought to determine if the lung releases lactate in humans and what relation this has with lung injury. METHODS: We measured lactate concentrations across the lung and lung injury scores (LIS) in two groups of patients. Group 1 consisted of nine patients with acute lung injury (LIS > or = 2.0) and elevated lactate concentrations (> 2.0 mmol/L). Group 2 contained 12 patients with no acute lung injury (LIS scores < or = 1.5), with or without increased lactate concentrations. Simultaneous measurements of plasma lactate and blood gases were obtained from indwelling arterial and pulmonary artery catheters. Measurements of cardiac output were also obtained. Lactate measurements were done using a lactate analyzer (YSI; Yellow Springs, Ohio). RESULTS: For each patient with acute lung injury and hyperlactatemia, an arterial-venous lactate gradient existed demonstrating release of lactate by the lung. This gradient persisted after correction for changes in hemoconcentration across the lung. The lactate gradient across the lung was 0.4 +/- 0.2 mmol/L for group 1 vs 0.05 +/- 0.1 mmol/L for group 2 (p = 0.001). This corresponded to a mean pulmonary lactate flux of 231.3 +/- 211.3 vs 5.0 +/- 37.2 mmol/h (p = 0.001). The lactate flux and the arterial-venous lactate difference correlated with LIS both for the entire sample and for the subgroup with hyperlactatemia (r = 0.69, p < 0.01). Pulmonary lactate flux was not related to arterial lactate levels (r = 0.25). CONCLUSION: In patients with acute lung injury and hyperlactatemia, the lung is a major source of lactate and lactate flux correlates with LIS. This lactate flux could explain some of the hyperlactatemia seen in sepsis.

Novel bioartificial liver support system: preclinical evaluation.

Preclinical safety and efficacy evaluation of a novel bioartificial liver support system (BLSS) was conducted using a D-galactosamine canine liver failure model. The BLSS houses a suspension of porcine hepatocytes in a hollow fiber cartridge with the hepatocytes on one side of the membrane and whole blood flowing on the other. Porcine hepatocytes harvested by a collagenase digestion technique were infused into the hollow fiber cartridge and incubated for 16 to 24 hours prior to use. Fifteen purpose-bred male hounds, 1-3 years old, 25-30 kg, were administered a lethal dose, 1.5 g/kg, of D-galactosamine. The animals were divided into three treatment groups: (1b) no BLSS treatment (n = 6); (2b) BLSS treatment starting at 24-26 h post D-galactosamine (n = 5); and (2c) BLSS treatment starting at 16-18 h post D-galactosamine (n = 4). While maintained under isoflurane anesthesia, canine supportive care was guided by electrolyte and invasive physiologic monitoring consisting of arterial pressure, central venous pressure, extradural intracranial pressure (ICP), pulmonary artery pressure, urinary catheter, and end-tidal CO2. All animals were treated until death or death-equivalent (inability to sustain systolic blood pressure > 80 mmHg for 20 minutes despite massive fluid resuscitation and/or dopamine administration), or euthanized at 60 hours. All animals developed evidence of liver failure at 12-24 hours as evidenced by blood pressure lability, elevated ICP, marked hepatocellular enzyme elevation with microscopic massive hepatocyte necrosis and cerebral edema, elevated prothrombin time, and metabolic acidosis. Groups 2b and 2c marginally prolong survival compared with Group 1b (pairwise log rank censored survival time analysis, p = 0.096 and p = 0.064, respectively). Since survival times for Groups 2b and 2c are not significantly different (p = 0.694), the groups were combined for further statistical analysis. Survival times for the combined active treatment Groups 2b and 2c are significantly prolonged versus Group 1b (p = 0.047). These results suggest the novel BLSS reported here can have a significant impact on the course of liver failure in the D-galactosamine canine liver failure model. The BLSS is ready for Phase I safety evaluation in a clinical setting.

Flow redistribution during progressive hemorrhage is a determinant of critical O2 delivery.

O2 consumption (VO2) of anesthetized whole mammals is independent of O2 delivery (DO2) until DO2 declines to a critical value (DO2c). Below this value, VO2 becomes O2 supply dependent. We assessed the influence of whole body DO2 redistribution among organs with respect to the commencement of O2 supply dependency. We measured DO2, VO2, and DO2c of whole body, liver, intestine, kidney, and remaining carcass in eight mongrel dogs during graded progressive hemorrhage. Whole body DO2 was redistributed such that the organ-to-whole body DO2 ratio declined for liver and kidney and increased for carcass. We then created a mathematical model wherein each organ-to-whole body DO2 ratio remained approximately constant at all values of whole body DO2 and assigned organ VO2 to predicted organ DO2 by interpolation and extrapolation of observed VO2-DO2 plots. The model predicted that O2 supply dependency without redistribution would have commenced at a higher value of whole body DO2 for whole body (8.11 +/- 0.89 vs. 6.98 +/- 1.16 ml.kg-1.min-1, P less than 0.05) and carcass (6.83 +/- 1.16 vs. 5.06 +/- 1.15 ml.kg-1.min-1, P less than 0.01) and at a lower value of whole body DO2 for liver (6.33 +/- 1.86 vs. 7.59 +/- 1.95, ml.kg-1.min-1, P less than 0.02) and kidney (1.25 +/- 0.64 vs. 4.54 +/- 1.29 ml.kg-1.min-1, P less than 0.01). We conclude that redistribution of whole body DO2 among organs facilitates whole body O2 regulation.

Hemodynamic effects of synchronous high-frequency jet ventilation in mitral regurgitation.

We tested the hypothesis that increases in intrathoracic pressure (ITP), by decreasing the pressure gradient for anterograde left ventricular (LV) ejection, should augment cardiac output in acute mitral regurgitation (MR). In a pentobarbital-anesthetized closed-chest canine model, LV stroke volume (SLLV) was measured by integration from an aortic flow probe signal. MR was induced by a regurgitant ring. ITP was elevated over apnea by means of intermittent positive-pressure ventilation (IPPV), asynchronous (asynch) high-frequency jet ventilation (HFJV), and cardiac cycle-specific (synch) HFJV. IPPV resulted in the greatest increase in ITP. MR caused a fall in SVLV and a rise in LV filling pressure that were not altered by IPPV. Compared with IPPV or apnea, both asynch and synch HFJV increased SVLV and reduced LV filling pressures (P less than 0.05). Systolic synch HFJV induced a greater increase in SVLV (32%) than diastolic synch HFJV (26%) despite similar ventilatory settings. Our data suggest that when LV contractility is normal but MR impairs forward flow, cardiac cycle-specific increases in ITP will augment forward flow.

Hepatic dysoxia commences during O2 supply dependence.

Hepatic O2 consumption (VO2) remains relatively constant (O2 supply independent) as O2 delivery (DO2) progressively decreases, until a critical DO2 (DO2c) is reached below which hepatic VO2 also decreases (O2 supply dependence). Whether this decrease in VO2 represents an adaptive reduction in O2 demand or a manifestation of tissue dysoxia, i.e., O2 supply that is inadequate to support O2 demand, is unknown. We tested the hypothesis that the decrease in hepatic VO2 during O2 supply dependence represents dysoxia by evaluating hepatic mitochondrial NAD redox state during O2 supply independence and dependence induced by progressive hemorrhage in six pentobarbital-anesthetized dogs. Hepatic mitochondrial NAD redox state was estimated by measuring hepatic venous beta-hydroxybutyrate-to-acetoacetate ratio (beta OHB/AcAc). The value of DO2c was 5.02 +/- 1.64 (SD) ml.100 g-1.min-1. The beta-hydroxybutyrate-to-acetoacetate ratio was constant until a DO2 value (3.03 +/- 1.08 ml.100 g-1.min-1) was reached (P = 0.05 vs. DO2c) and then increased linearly. Peak liver lactate extraction ratio was 15.2 +/- 14.1%, occurring at a DO2 of 5.48 +/- 2.54 ml.100 g-1.min-1 (P = NS vs. DO2c). Our data support the hypothesis that the decrease in VO2 during O2 supply dependence represents tissue dysoxia.

Renal O2 consumption during progressive hemorrhage.

Most mammalian tissues regulate O2 utilization such that O2 consumption (VO2) is relatively constant at O2 delivery (DO2) higher than a critical value (DO2c). We studied the relationship between VO2 and DO2 of kidney and whole body during graded progressive exsanguination. The relationship between whole body VO2 and DO2 was biphasic, and whole body VO2 decreased by 5.6 +/- 14.4% (P = NS) from the initial value to the value nearest whole body DO2c. Kidney DO2 decreased in direct proportion to whole body DO2 such that the average R2 value describing the linear regression of kidney DO2 vs. whole body DO2 was 0.94 +/- 0.02. The relationship between kidney, like whole body, VO2 and DO2 appeared biphasic; however, kidney VO2 decreased by 63.3 +/- 10.4% (P less than 0.0001) from the initial value to the value nearest kidney DO2c. Renal O2 extraction ratio was relatively constant over a wide range of kidney DO2, whereas whole body O2 extraction ratio increased progressively at all whole body DO2 values as whole body DO2 decreased. However, final values of O2 extraction ratio were indistinguishable for whole body (0.86 +/- 0.1) and kidney (0.86 +/- 0.06) (P = NS). We conclude that the pattern of kidney and whole body VO2 response to decreasing DO2 differs during hemorrhage, particularly in the range of DO2 normally associated with tissue wellness.

Hepatic anion flux during acute endotoxemia.

We sought to determine the role the liver might play in the regulation of anion-cation balance during both stable baseline conditions and acute endotoxemia. Ten pentobarbital sodium-anesthetized dogs were instrumented at laparotomy with ultrasonic flow probes around the left renal artery, portal vein, and hepatic artery, and catheters were inserted into the hepatic vein, portal vein, pulmonary artery, left renal vein, and abdominal aorta. Measurements were obtained from each site at baseline and 30-45 min after the intravenous infusion of endotoxin. The total anion flux across the liver was calculated from the strong-ion difference. At baseline, the liver removed anions from the circulation (-0.34 meq/min). With early endotoxemia, however, the liver switched to the release of anions (0.12 meq/min; P = 0.0046). After endotoxin administration, the gut, which was neutral at baseline, began to take up anions (-0.47 meq/min; P = 0.008). Anion flux across the lung and kidney was unchanged. We conclude that in the dog the liver, which removes anions at baseline, switches to release anions during early endotoxemia and may be a major site of acid production in early sepsis.

Intraoperative ultrasound guidance for intrauterine endoscopic surgery.

Intraoperative US guidance for intrauterine endoscopic procedures appears to offer a noninvasive means of assessing the precision and adequacy of resectoscopic myomectomy and to provide the exact location of the instruments within the uterine cavity and uterine wall. A combination of intrauterine endoscopic procedures and intraoperative US guidance provides an accurate method to guide resectoscopic myomectomies and endometrial resection and to prevent inadvertent uterine perforation. Intraoperative imaging may have an application for other intrauterine endoscopic procedures and may preclude the need for simultaneous laparoscopy.

Fulminant hepatic failure.

Fulminant hepatic failure is a disease of varied causes and a high mortality rate. A sudden onset, jaundice, hepatic encephalopathy, and multiorgan failure are the hallmarks of this syndrome. The management of patients with FHF requires a multidisciplinary approach and intense monitoring. The availability of liver transplantation has provided the means to rescue such patients from near-certain death. Early prognostication and timely availability of donor livers are requirements for a successful outcome. The development of effective artificial liver support devices may greatly prolong the window of opportunity to provide a donor liver, or alternatively, to allow the native liver to regenerate.

Early complications after orthotopic liver transplantation.

The cost and impact of early post-transplant complications continue to be high. Diagnosis and management involves a high index of suspicion, rapid diagnostic and therapeutic interventions, and elimination of technical problems. Preoperative assessment of the donor and recipient medical condition and meticulous attention to detail during the technical performance of OLTx are the mainstays in achieving a good outcome.

Splanchnic buffering of metabolic acid during early endotoxemia.

PURPOSE: We sought to determine the sites of metabolic acid production and clearance during acute endotoxemia. MATERIALS AND METHODS: In 10 pentobarbital-anesthetized dogs, flow was measured (ultrasonic probes) for the protal vein, hepatic artery, and renal artery. Catheters were inserted into the hepatic vein, pulmonary artery, renal vein and portal vein. Measurements of blood gases and strong ions were obtained from each site during control conditions and after 30 minutes of intravenous infusion of 1 mg/kg of Escherichia coli endotoxin. The total metabolic acid flux across each organ was calculated using the standard base excess formula and the effective strong ion difference method. PaCO2 was maintained by controlled ventilation. RESULTS: Mean arterial pH decreased from 7.34 to 7.22 with acute endotoxemia. Although transvisceral pH gradients revealed net acid release, the source of this was purely respiratory (carbon dioxide). During early endotoxemia, the gut significantly increased metabolic acid uptake (36.60 +/- 6.60 mmol/h, P < .05). CONCLUSIONS: We conclude that during early endotoxemia in the dog, the gut is a major site of metabolic acid removal.

Strong ion gap: a methodology for exploring unexplained anions.

PURPOSE: This paper describes the calculation of the strong ion gap (SIG), a physical chemical methodology similar to the anion gap (AG), as a measure of the anion/cation balance exclusive of sodium, potassium, chloride, and bicarbonate. We compared the SIG and AG methodologies in three groups of subjects with and without unexplained anions. These groups were (1) healthy volunteers with hyperlacticemia during exercise; (2) intensive care unit (ICU) patients with sepsis; and (3) ICU patients with severe liver disease. METHODS: The SIG, AG, and corrected AG (AGc) were calculated for each group from data available in the original reports (groups 1 and 2) and by retrospective chart review (group 3). RESULTS: The SIG correlated poorly with the AG in group 2, whereas no correlation was seen in groups 1 and 3. The AGc correlated with SIG in all three groups (r = .99, .93, and .91 respectively; P < .01 for each group). Although the AG was similar, the SIG differed for each group. Group 1 had levels of SIG near zero, and groups 2 and 3 had mean SIG's of 4.80 +/- 4.67 mEq/L and 9.60 +/- 6.43 mEq/L respectively. The composition of the anion gap differed markedly among subject types. CONCLUSIONS: The SIG correlates with the AG once corrected for all known anions. The SIG technique can detect unknown anions in a patient population known to have them and does not detect unknown anions in healthy volunteers during exercise. This test detects large amounts of unknown anions in some patients with sepsis or liver disease. Therefore, the test is both sensitive and specific in characterizing metabolic acidosis.

Management options in fulminant hepatic failure.

The diagnosis of FHF carries with it a high mortality rate. Though the early results of OLT for FHF are encouraging, some have called for caution as these results are in a select population and may be similar to the optimistic early reports of now-discredited therapies. However, OLT differs fundamentally from all other interventions and, as such, it is ethically unjustified to withhold potentially life-saving therapy from patients with a predicted mortality in excess of 60%. Therefore, patients with FHF should be transferred at an early stage to an experienced liver unit where the option of liver transplantation can be considered.

Comparison of fever treatments in the critically ill: a pilot study.

BACKGROUND: Fever in critically ill patients is often treated with antipyretics or physical cooling methods. Although fever is a host defense response that may benefit some critically ill patients, others may not tolerate the cardiovascular demands associated with fever. OBJECTIVES: To compare antipyretics and physical cooling for their effects on core body temperature and cardiovascular responses in critically ill patients. METHODS: The antipyretic administered was 650 mg of acetaminophen. Physical cooling was accomplished by anterior placement of a cooling blanket at 18 degrees C. Core temperature and cardiovascular responses were measured in 14 febrile (body temperature, 38.8 degrees C) critically ill patients at baseline before treatment and up to 3 hours after treatment. Patients able to receive acetaminophen were randomly assigned to receive either acetaminophen only (n = 5) or acetaminophen in combination with a cooling blanket (n = 3). Patients not able to receive acetaminophen were treated with physical cooling only (n = 6). RESULTS: Mean body temperature decreased minimally from baseline to 3 hours after treatment in the physical-cooling-only group (from 39.1 degrees C to 39.0 degrees C) and in the physical cooling and acetaminophen group (from 39.1 degrees C to 38.6 degrees C), but the mean body temperature increased in the acetaminophen-only group (from 39.2 degrees C to 39.4 degrees C). Other notable findings included a slight increase in systemic vascular resistance index in the physical-cooling-only group and in the physical-cooling-plus-acetaminophen group. CONCLUSIONS: Although the study included only 14 subjects, the findings will provide information for future studies in febrile critically ill patients.

Amniotic fluid volume: fluid dynamics and measurement technique.

Evaluation of amniotic fluid volume is an important aspect of obstetrical ultrasound. Several methods are currently used to describe amniotic fluid volumes. The most common are the subjective assessment of fluid and the semiquantitative methods. The reproducibility of these methods is excellent in experienced hands. Because of the multiple methods used to assess fluid, both oligohydramnios and polyhydramnios have numerous definitions. Regardless of which definition is used, it is clear that both of these entities are associated with a variety of fetal and maternal conditions. Abnormal amniotic fluid volume may be the only or earliest sonographic sign of an obstetrical problem. Therefore, it is important that sonologists are familiar with amniotic fluid volume assessment. Although subjective and semiquantitative techniques may produce similar results, a numerical scale is no substitute for experience and training. One should be able to recognize lesser degrees of fluid abnormality and be able to assess the trend of amniotic fluid volume in serial examinations.