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Biomedical subjects

F B Cerra

Publications and source records attributed to F B Cerra.

At least 181 records · Page 10Linked to original sources
PubMed1982

Branched chains support postoperative protein synthesis.

A blinded, prospective trial of the effects of branched-chain amino acid (BcAA)-enriched total parenteral nutrition (TPN) versus standard TPN was undertaken in nonseptic noncirrhotic abdominal surgery patients and patients with multiple traumatic injuries. The study reflected data from the immediate 7-day postoperative period. With isocaloric and isonitrogenous input, the BcAA-TPN patients achieved positive nitrogen balance on day 3. Although the urinary nitrogen output was decreased by day 3 in BcAA-TPN, the plasma BcAA levels did not increase until day 6. With no change in 3-methylhistidine urinary excretion, the early nitrogen retention with BcAA-TPN probably reflects a stimulation of protein synthesis. The ability to favorably modulate the metabolic stress response with alternate fuels has become a clinical reality.

Adult↗
PubMed1981

Death after portal decompressive surgery. Physiologic state, metabolic adequacy, and the sequence of development of the physiologic determinants of survival.

Detailed serial cardiovascular and respiratory physiologic studies were carried out in 80 patients with cirrhotic liver disease, including 45 cirrhotic patients who underwent portal decompressive surgery on an urgent or elective basis. In surgical cases, death could be predicted from the first postoperative day's pattern of response. Predictors of death were an increase in percent of pulmonary shunt due to a redistribution of the increased pulmonary blood flow, and a disproportionate fall in vascular tone, which permits an increased cardiac ejection fraction even when significant myocardial depression occurs. The etiology of the vascular tone defect seems related to the rise in levels of the false neurotransmitter octopamine, which are shown to increase as oxygen consumption falls in the patho-physiologic hyperdynamic B state, presumably due to a block in the oxidative metabolism of aromatic amino acids.

Esophageal and Gastric Varices↗
PubMed1981

Arterial embolization for traumatic hemobilia with hepato-portal fistula.

A case of blunt liver trauma complicated by delayed upper gastrointestinal bleeding, probably hemobilia, was successfully treated by intra-arterial embolization. Laparotomy with liver resection or hepatic artery ligation--procedures that carry a high morbidity and mortality in a critically ill patient--were avoided. Embolization techniques can be a valuable alternative to surgery in the management of hepatic trauma with delayed hemorrhage in selected, high-risk cases.

Adult↗
PubMed1981

Age, disease, and cimetidine disposition in healthy subjects and chronically ill patients.

Cimetidine induces reversible dose-related central nervous system (CNS) toxicity. Trough serum concentrations and the development of CNS toxicity correlate. We compared cimetidine kinetics in 12 healthy subjects and 31 patients. Six of the latter had normal renal and liver function, five had renal disease only, 12 had liver disease only, and eight had both renal and liver disease. Postmortem tissue distribution was assessed in 11 patients, and expressed as tissue:serum ratio. Average cimetidine total clearance (ClB) in milliliters per minute for each group was as follows: patients with renal and liver disease (182 +/- 105), renal disease only (193 +/- 24), liver disease only (463 +/- 145), normal patients (510 +/- 93), and healthy subjects (583 +/- 140). Renal function was the major determinant for ClB, and the relationship was described by ClB = 4.2(CCr) + 140, r = 0.87, where CCr is creatinine clearance. Cimetidine clearance was affected little by age. Tissue:serum ratios from highest to lowest were as follows: kidney greater than stomach greater than liver greater than bone greater than brain greater than fat. Central and steady-state distribution volumes were not influenced by age or disease. There was enchanced CNS penetration in liver disease patients; their cerebrospinal fluid (CSF):serum ratio was twice the normal. Our kinetic studies identify patient characteristics likely to result in elevated blood levels, and suggest that the greatest risk of CNS toxicity is in those with liver disease.

Adolescent↗
PubMed1981

Progressive necrotizing surgical infections--a unified approach.

Four types of progressive necrotizing surgical infections have been described, based on the type of infecting organism, the type and depth of soft tissue penetration and clinical findings, and the type of surgical therapy recommended, e.g., necrotizing fasciitis, clostridial cellulitis. A mortality rate of up to 50% continues to be reported. An experience with 20 such cases indicates that there is a considerable overlap in clinical-physical findings and bacteriology such that classification schemes are confusing and lead to treatment delays and the use of inappropriate therapy. The infections all seem to be variations of the same disease process, a spreading, necrotizing infection. Of the 20 cases, four were treated with antibiotics and delayed (1 to 3 days) excision of necrotic tissue with 75% deaths; four cases received antibiotics and multiple surgical incisions with 100% deaths. The other 12 cases were treated with a unified approach of resuscitation, antibiotics (penicillin, clindamycin, tobramycin), immediate surgical excision (3 to 4 hours) of all necrotic tissue, aggressive nutritional support, and early skin coverage, with an 8.3% mortality. We conclude that there seems to be no need to classify necrotizing infections into different types. Recognizing them as the same disease process and treating them with a unified approach resulted in a significant reduction in mortality.

Adult↗
PubMed1981

Amikacin and gentamicin accumulation pharmacokinetics and nephrotoxicity in critically ill patients.

Twenty-five critically ill adults receiving blood level-adjusted doses of amikacin were prospectively studied with serum, urine, and, when possible, tissue amikacin concentrations. These data were fitted to a two-compartment pharmacokinetic model. Prolonged urine collections or postmortem tissues (or both) were used to confirm predicted tissue accumulation. Nephrotoxicity was also investigated. Patients were defined as having renal damage if they showed an increase in serum creatinine of greater than 0.5 mg/100 ml, an increase in urine beta 2-microglobulin of greater than 50 mg/day, and presence of urinary casts of greater than 500/ml. Renal damage was attributed to amikacin if there was, in addition to the above, tissue accumulation of amikacin of greater than 600 mg. These patients were matched with 25 patients treated with gentamicin during the same time period. There were no statistical differences between the gentamicin- and amikacin-treated patients in age, sex, weight, base-line creatinine clearance, concurrent cephalosporins or diuretics, treatment duration, site of infection, normalized (amikacin/gentamicin dosing ratio of 3:1) total dose, mortality, or tissue accumulation. More amikacin-treated patients (19 of 25) than gentamicin-treated patients (9 of 25) received prior aminoglycosides (P less than 0.01). The only pharmacokinetic parameter that differed between amikacin and gentamicin was a greater K21 for gentamicin. Nephrotoxicity was observed in 4 gentamicin was a greater K21 for gentamicin. Nephrotoxicity was observed in 4 gentamicin-treated patients (16%) and 5 amikacin-treated patients (20%). At a 3:1 dosing ratio, there were no significant differences between amikacin and gentamicin two-compartment pharmacokinetics and nephrotoxic potential in matched critically ill patients, but the trend of these data showed greater amikacin tissue accumulation. However, at an amikacin/gentamicin dosing ratio of 4:1, their tissue accumulation potential appeared to be almost identical.

Amikacin↗
PubMed1981

Comparative nephrotoxicity of gentamicin and tobramycin: pharmacokinetic and clinical studies in 201 patients.

A total of 201 critically ill patients were studied during 267 courses of gentamicin or tobramycin treatment (139 gentamicin courses and 128 tobramycin courses). Of these 267 courses, pharmacokinetic and clinical data were obtained for 240 (120 gentamicin and 120 tobramycin). The data collected for pharmacokinetic analysis included measurements of serial blood and urine levels, urinary excretion of beta 2-microglobulin, protein levels, and granular casts. A two-compartment model was used to assess tissue accumulation, and in 89 courses the predicted accumulation was confirmed by cumulative urine collection or postmortem tissue analysis. As groups, the patients given gentamicin and tobramycin did not differ in age, weight, creatine clearance, total dose given, duration of treatment, initial aminoglycoside through serum levels, number of dosage adjustments, concurrent use of furosemide, or concurrent cephalosporins. Previous aminoglycoside treatment (usually gentamicin) had occurred more frequently in the tobramycin treated patients (P less than 0.01), and more males than females received tobramycin (P less than 0.05). Pharmacokinetic assessments of renal damage were based on both changes in glomerular filtration rate (serum creatinine levels, creatinine clearance) and renal tubular damage (beta 2-microglobin, casts), but only patients with elevated aminoglycoside tissue levels leading to renal tubular damage and subsequent creatinine clearance decreases were considered to have experienced aminoglycoside nephrotoxicity. In the pharmacokinetic analysis of nephrotoxicity, 29 gentamicin courses (24%) and 12 tobramycin courses (10%) were complicated by nephrotoxicity (P less than 0.01). The 201 study patients were also evaluated independently for clinical nephrotoxicity (defined as a serum creatinine level increase of 0.5 mg/dl or more). Clinical nephrotoxicity occurred at rates of 37% in the gentamicin-treated group and 22% in the tobramycin-treated group (P less than 0.02). In these similar groups of critically ill patients, tobramycin was less nephrotic than gentamicin.

Aged↗
PubMed1981

Multiple systems organ failure: V. Alterations in the plasma protein profile in septic trauma - effects of intravenous amino acids.

The correlations between the acute phase and nutritional plasma proteins and intravenous amino acid dosage have been explored in a group of 25 trauma septic patients of whom 14 survived. The two groups of patients appeared to have equal cardiopulmonary function and exogenous nutritional support. The surviving group showed significant associated changes (p less than or equal to 0.05) between alpha1 acid glycoprotein, alpha2 HS glycoprotein, and ceruloplasmin (acute-phase proteins) and between prealbumin, retinol-binding protein, and transferrin (nutritional proteins). There were no correlations in concentration changes between these two groups of plasma proteins. The surviving group showed significant positive correlations between the nutritional plasma protein and intravenous amino acid dosage (prealbumin, p less than or equal to 0.001; transferrin, p less than or equal to 0.008; retinol-binding protein, p less than or equal to 0.001; and albumin, p less than or equal to 0.004) but no correlations with the acute-phase proteins. The nonsurviving patients showed significant intercorrelations between the acute-phase and nutritional proteins that were not seen in the surviving patients, and showed no relationship between intravenous amino acid dosage and the plasma levels of nutritional proteins. The data are consistent with increased obligatory catabolism of amino acids in the nonsurviving patient which based upon the amino acid behavior documented in the first paper in this series probably involves the branched-chain amino acids.

Amino Acids↗
PubMed1981

Multiple systems organ failure: II. The effect of infusion of amino acids and glucose.

Amino acids and dextrose infusion were given for short periods of time to a young man whose basal state is characterized in the previous paper in this series, and their effects were documented in terms of plasma concentrations and splanchnic extraction. The basal state measurements show in the acute trauma state and its subsequent starvation state a largely balanced splanchnic extraction of amino acids but at a decreasing rate. Amino acid (FreAmine) infusion at low rates on this background produced a large increase in extraction of a largely balanced mixture of amino acids but a minimal change in glucose release. The septic state is characterized in both the basal and amino acid infusion state by splanchnic extraction of an unbalanced mixture of amino acids which is deficient in branched-chain amino acids and in relative excess of glucogenic amino acids with increased glucose release and increased utilization of amino acids for gluconeogenesis. In early sepsis this state can largely be repaired by exogenous amino acid infusion but in late sepsis can only be partially repaired. The data suggest that the patient in late sepsis should have a branched-chain rich amino acid mixture and that the hepatic failure of sepsis is strongly associated with peripheral release of an unbalanced mixture of amino acids secondary to enhanced branched-chain catabolism. Infused glucose produces a large increase in the plasma glucose but also improves the balance of the splanchnic amino acids extracted. The statistical validity of the preceding statements are examined in detail in the manuscript.

Amino Acids↗
PubMed1981

Multiple systems organ failure: III Contrasts in plasma amino acid profiles in septic trauma patients who subsequently survive and do not survive-effects of intravenous amino acids.

The response of the plasma substrate and hormone profile of survivor and nonsurvivor septic trauma patients to varying rates of amino acid infusion (IVAA) were contrasted. When IVAA=0 levels of most plasma amino acids (except aspartate, tryptophan, cysteine, and proline) were lower in nonsurvivors. At IVAA=1 to 100, however, 11 of 20 plasma amino acids were significantly (p less than or equal to 0.05) higher in nonsurvivors: only glutamate was significantly lower (p less than or equal to 0.001) and valine, isoleucine, and arginine on average lower. At IVAA less than or equal to 101 to 200, only alanine, methionine, tyrosine, and phenylalanine were significantly (p less than or equal to 0.005) higher in nonsurvivors; isoleucine was significantly (p less than or equal to 0.02) lower. The sharp increase in methionine and decrease in tryptophan in nonsurvivors with IVAA was particularly marked. Polynomial regression analysis showed that urea increased significantly with IVAA in both patient groups, while free fatty acids and cortisol decreased only in nonsurvivors. Insulin increased with IVAA only in survivors, glucagon only in nonsurvivors. Triglycerides, glycerol, acetoacetate, beta OH butyrate, and glucose appeared to show no significant response to IVAA in either patient group. The data are consistent with increased peripheral protein catabolism and branched-chain amino acid oxidation in association with decreased tissue uptake of conventional energetic fuels. These results may be interpreted to be consistent with an impairment of mitochondrial translocase systems.

Adolescent↗
PubMed1981

Multiple systems organ failure: IV. Imbalances in plasma amino acids associated with exogenous albumin in the trauma-septic patient.

In a survey study of septic trauma patients, the response of plasma amino acid concentration to albumin infusion was contrasted in survivors (14 patients) and nonsurvivors (11 patients). Plasma albumin levels were maintained at 3 gm/dl by albumin infusion (0-128 gm/day) because of central venous pressure/adequate circulation considerations. Survivors showed no significant increase in plasma essential amino acid concentration as a function of albumin infusion. In nonsurvivors threonine, valine, leucine, phenylalanine, lysine, and histidine all rose significantly (p less than or equal to 0.025) with albumin infusion. Isoleucine (8 residues/molecule albumin), in contrast to leucine (60 residues/molecule) did not increase. As a result, the ratio of isoleucine to leucine (Ile/Leu) decreased with albumin infusion from 0.47 (no albumin infused) to 0.27 (60 gm albumin/day). Survivors did not exhibit a similar response. The low Ile/Leu increased in most nonsurvivors with amino acid infusion from 0.27 (no amino acids) to 0.59 (150 gm amino acids/day). The data strongly suggest that nonsurvivors had an increased rate of albumin catabolism with subsequent amino acid release. Moreover, hypoalbuminemia treated with albumin infusion without amino acid infusion appears to produce a relative isoleucine deficiency which may detrimentally affect protein synthesis.

Accidents, Traffic↗
PubMed1980

Septic autocannibalism. A failure of exogenous nutritional support.

Forty-six patients with surgical sepsis were studied prospectively until death or survival to evaluate the effect of exogenous metabolic support on the observed plasma substrate levels and on the differential endogenous utilization of branch chain amino acids. There were no effects of administered glucose or colloid load. The administered amino acid load had little effect on substrate levels in patients who died; but significantly effected the observed levels of glycine, isoleucine, and methionine in patients who survived. Evidence is presented which suggests that fatal sepsis is associated with an increased release of endogenous valine and isoleucine into plasma, as well as increased plasma levels of tyrosine, proline, and methionine. These abnormalities are highly correlated with the increased levels of plasma alanine and occur at a time when the nonsurviving septic patient manifests a tendency toward reduced oxygen consumption and abnormal vascular tone relations--the septic B state. These data are consistent with the hypothesis that increased muscle protein catabolism is occurring with a differential utilization of branch chain amino acids and increased use of leucine and isoleucine and reduced use of valine. This autocannibalism of muscle mass appears to be the source of the increased plasma alanine and is little influenced by administered amino acid support in the absence of control of the septic process.

Alanine↗
PubMed1980

The systemic septic response: does the organism matter?

The clinical and physiological responses to septicemia were evaluated in 59 patients with 70 septic episodes. All patients were critically ill, had similar ICU support, and had positive blood cultures as well as a clinical infection when studied by dye dilution cardiac outputs. The overall ratio of gram-negative to gram-positive sepsis was 2.6:1.0. Patients with septicemia caused by gram-positive organisms, gram-negative organisms, anaerobes, and fungi had similar fever, leucocyte, and acid-base responses. There were also no statistical differences in any physiological variables between organism group or between specific organisms. After volume loading, all patients exhibited a hyperdynamic cardiovascular response with abnormal vascular tone. Some degree of myocardial depression was a common feature of all forms of bacterial or fungal septicemia. Heart rate was the cardiac variable producing the increased cardiac output in this setting. The exact pathogenesis of the septic response remains undetermined. However, the response appears to be host determined and not peculiar to a specific pathogenic microorganism.

Adult↗
PubMed1980

Dose and serum concentration relationships in cimetidine-associated mental confusion.

A patient with severe liver disease and mildly obnormal but stable renal function was given cimetidine on two occasions for gastrointestinal hemorrhage. In each course, dosing was initiated at half the recommended dosage of 600 mg daily, and mental status deteriorated shortly after dosing began. A further dosage decrease to 300 mg daily allowed continuation of cimetidine therapy in absence of mental status alterations. In this patient, mental status changes occurred at lower serum concentrations than we have previously reported. This discrepancy was explained by analysis of cimetidine CSF concentrations, as this patient had abnormally high cimetidine blood to CSF permeability. Although the cause of increased CSF concentrations is unclear, cimetidine-associated mental confusion was dose related and completely reversible upon a decrease in dosage. Patients who develop cimetidine-associated mental status changes and who cannot have treatment stopped may be safely treated by individualizing the dosing rate.

Blood-Brain Barrier↗
PubMed1980

Effect of hemodialysis on total body clearance of chloramphenicol.

The effect of hemodialysis on the total body clearance (ClTB) of chloramphenicol was studied in two patients with renal failure and hepatic dysfunction. Chloramphenicol sodium succinate was administered intravenously eight hours before dialysis in doses of 20 and 26.1 mg/kg/day to Patients 1 and 2, respectively. Serum samples were taken at 48 hours after initiation of the drug, 2.5 hours after the last dose and 5 minutes into dialysis for Patient 1, and before dosing and at 0.5, 1, 2, 4, 6, 8 and 11 hours after dosing for Patient 2. Serum levels of chloramphenicol were measured by high-performance liquid chromatography. Chloramphenicol ClTB values on dialysis (162.2 and 118 ml/min for Patients 1 and 2, respectively) were 58% and 72% higher than off-dialysis ClTB values (102.9 and 69 ml/min) for Patients 1 and 2, respectively. Dialysis extraction ratios for chloramphenicol were 0.52 and 0.31 for Patients 1 and 2, respectively. Although the increased clearance of chloramphenicol that occurred during dialysis may be important only in patients with hepatic dysfunction, it is recommended that the normal maintenance dose of the drug be administered after dialysis to avoid the possibility of increased clearance.

Adult↗
PubMed1979

Pharmacokinetic and clinical studies in patients with cimetidine-associated mental confusion.

15 cases of cimetidine-associated mental confusion have been reported. In order that this syndrome might be investigated changes in mental status (M.S.) were correlated with serum concentrations and renal and hepatic function in 36 patients, 30 patients had no M.S. change on cimetidine and 6 had moderate to severe changes. These 6 patients had both renal and liver dysfunction (P less than 0.05), as well as cimetidine trough-concentrations of more than 1.25 microgram/ml (P less than 0.05). The severity of M.S. changes increased as trough-concentrations rose, 5 patients had lumbar puncture. The cerebrospinal fluid: serum ratio of cimetidine concentrations was 0.24:1 and indicates that cimetidine passes the blood-brain barrier; it also raises the possibility that M.S. changes are due to blockade of histamine H2-receptors in the central nervous system. Patients likely to have both raised trough-concentrations and mental confusion are those with both severe renal and hepatic dysfunction. They should be closely observed and should be given reduced doses of cimetidine.

Aged↗