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Query: UMLS:C0036690 (sepsis)
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This paper describes work to develop a model-based system to support clinical decision-making. In previous articles, we have developed (from 695 measurement sets obtained from 148 patients) a physiologic state classification based on a set of 11 cardiovascular and metabolic measurements. There is an R or reference state, for stable ICU patients. Patients under (operative, traumatic, or compensated septic) stress, or with (septic or hepatic) metabolic, respiratory, or cardiac insufficiency are in the A, B, C, or D states, respectively. We wished to make the state easier to measure and eventually available continuously, automatically, and noninvasively, as well as reflecting a wider group of bodily systems. The 5 centers define a 4 dimensional affine subspace, designated the cardiovascular state space. Using eigenvector analysis, we have found four new derived physiologic variables CV1, CV2, CV3, and CV4 that span the state space. We have fit sets of linear regression equations that allow the patient's position in the state space, and therefore his state, to be determined from more easily obtainable sets of measurements. Further, we selected 1966 measurement sets from 512 patients at two hospitals. We used the data from 250 of these patients to define 13 prototypical types, namely survivors and deaths from various combinations of sepsis, cardiogenic decompensation, cirrhosis, and pneumonitis, following trauma or general surgery. For any future patient, the statistical theory of Bayesian inference allows one to infer back from the measurements observed to the probability of his being of any of these types and of surviving or dying. We used this method to predict the outcome of the other 262 patients, prospectively. Statistically, the predictions of survival or death were not significantly different from the actual. For individual patients, the method predicts a clinical course that closely follows the actual episodes in their history. These results confirm and explain the validity of the concept of the patient state and make the state easier to compute. The patient state and the probability plot together help to stage, select, and evaluate therapy. They do not replace the clinician's judgement, but rather are tools that help the clinician to exercise judgement.
Int J Clin Monit Comput 1990
PMID:Probability and the patient state space. 209 69

Fiberoptic pulmonary artery catheters provide a practical method for continuously measuring the amount of oxygen in mixed venous blood. To characterize the usefulness of mixed venous oxygen saturation in managing patients with sepsis, we performed serial hemodynamic measurements on 20 patients with documented septic shock. There was a highly significant positive correlation between increases or decreases of 5% or more in mixed venous oxygen saturation and corresponding changes in oxygen delivery (r = 0.95) and oxygen consumption (r = 0.96). Mixed venous oxygen saturation less than 65% was clinically unacceptable in patients with sepsis and was associated with a poor prognosis. In this study, measurement of mixed venous oxygen saturation was a valuable predictor of survival in patients with septic shock and provided a means of continuously monitoring the status of tissue oxygenation.
J Clin Monit 1986 Oct
PMID:Continuous monitoring of mixed venous oxygen saturation in septic shock. 309 69

The single breath test for carbon dioxide (SBT-CO2) is the plot of expired FCO2 or CO2% against expired volume. It can be monitored during anaesthesia and in the intensive care unit with modest additions to generally available equipment. This paper describes some aspects of a computer program for presenting SBT-CO2 during controlled ventilation, in particular, the corrections to the primary data necessary for scientific accuracy. Examples are given of how the use of SBT-CO2 has increased our understanding of factors which influence the arterial-end-tidal PCO2 difference (PaCO2-PE,CO2). PaCO2-PE, CO2 is, in a given individual, usually dependent on tidal volume and frequency. Changes in lung volume and manoeuvres such as opening the pleura also affect gas exchange. Monitoring CO2 elimination gives a measure of metabolic rate if ventilation and pulmonary perfusion are maintained. This facilitates ventilatory therapy in situations where CO2 production is greatly increased, e.g. sepsis and tetanus. On the other hand, if metabolism and ventilation are unchanged, a reduction in CO2 elimination implies reduced pulmonary perfusion. This can be seen during increased right-left shunting, such as in surgery in patients with congenital heart disease.
Int J Clin Monit Comput 1986
PMID:On-line expiratory CO2 monitoring. 309 79

The microbiological risk of invasive hemodynamic monitoring was studied prospectively in 230 consecutive patients undergoing cardiac valve replacement during prophylactic therapy with cephalothin. A total of 923 catheter tips were cultured, and 1.6% yielded positive cultures. The rate of positive cultures did not differ significantly between catheters inserted percutaneously (1.9% positive) and those inserted surgically (0.5% positive). The incidence of positive catheter tip cultures for intravenous, central venous, arterial, and pulmonary arterial catheters was 0, 1.5, 2.6, and 2.9%, respectively, whereas the surgically inserted right and left atrial catheters yielded 0.6 and 0% positive tip cultures, respectively. One patient developed septicemia related to a right atrial catheter. There was no correlation between the incidence of positive catheter tip cultures and the length of time that the catheters remained in situ. No patient developed early or late endocarditis. Invasive hemodynamic monitoring seems to be microbiologically safe, even in patients undergoing cardiac valve replacement.
J Clin Monit 1986 Apr
PMID:The microbiological risk of invasive hemodynamic monitoring in adults undergoing cardiac valve replacement. 371 52

The preferred dose of netilmicin was determined in each of 39 patients with severe gram-negative sepsis treated at two centres. The dose was based upon the attainment of recommended serum concentrations. Patient age varied from 18 to 87 years (mean 58), estimated creatinine clearance from 20 to 150 ml/min (mean 71), and the preferred dose from 100 to 750 mg/24 h. The dose generated by a nomogram for netilmicin was compared in retrospect with the initial dose assigned to each patient by the clinical microbiologist concerned. With respect to the preferred dose, the nomogram underdosed, on the average, by 40 mg/24 h, and the microbiologists, by 30 mg/24 h. The correlation with the preferred dose was stronger for the nomogram dose (r = 0.66; p less than 0.001, 37 df) than for the microbiologists' dose (r = 0.47; p less than 0.005, 37 df) but there was no significant difference between the two in the frequency with which they predicted the preferred dose to within 50 mg/24 h (nomogram 19/39; microbiologists 16/39). The prescription of a fixed dose of 450 mg/day to all patients would have had a similar success rate (15/39). The performance of the nomogram was better in patients with serum creatinine concentrations of greater than or equal to 100 microM (r = 0.82; p less than 0.001, 13 df; 10/15 within 50 mg/24 h of preferred dose) than in those with creatinine concentrations less than 100 microM (r = 0.55; p less than 0.01, 22 df; 9/24 within 50 mg/24 h of preferred dose).
Ther Drug Monit 1986
PMID:Netilmicin in gram-negative sepsis: comparative abilities of a dosage nomogram and clinical microbiologists to predict the preferred individual dose. 382 30

Amikacin, a semisynthetic analog of kanamycin, is very active against most gram-negative bacteria including gentamicin- and tobramycin-resistant strains. The effectiveness of amikacin in the treatment of serious gram-negative bacillary infections is well documented. Due to its resistance to inactivating enzymes, it is the aminoglycoside of choice for the treatment of known or suspected serious gram-negative infections caused by organisms resistant to gentamicin or tobramycin. Amikacin should be part of an empiric antibiotic regimen for the therapy of suspected sepsis in febrile, leukopenic immunocompromised hosts since it exhibits enhanced activity against the organisms most frequently encountered in this patient population. High response rates have been reported with the use of amikacin combined with beta-lactam antibiotics in immunocompromised or granulocytopenic patients. It exhibits impressive in vitro synergy against aminoglycoside-sensitive and -resistant organisms when used in combination with the new acylureidopenicillins and third-generation cephalosporins. Amikacin has the advantage of being the aminoglycoside least inactivated by the semisynthetic penicillins. Amikacin achieves high and predictable serum concentrations and has a favorable therapeutic index. Its potential for nephrotoxicity and ototoxicity is not significantly different than that encountered with gentamicin or tobramycin. Amikacin appears to be the preferred aminoglycoside for use at the present time because of its activity against gentamicin- and tobramycin-resistant organisms, its low resistance potential, its relative low degree of inactivation by the semisynthetic penicillins, and its superior pharmacokinetic profile.
Ther Drug Monit 1985
PMID:An overview of amikacin. 388 67

A computer based evaluation system has been developed for the assessment of respiratory pressure flow dynamics, pulmonary gas exchange and ventilation perfusion interrelationships. This system is based on the acquisition of primary data on-line from intubated and ventilated patients consisting of airway pressures, ventilatory flows and mass spectrometric quantification of inspired and expired gas concentrations. The system has been applied to the study of patients with the adult respiratory distress syndrome (ARDS) following trauma and/or sepsis. The programs developed for evaluation of these data permit an interactive graphic capability to be used by the physician or the respiratory technician in a specific patient to determine the nature of the abnormalities in respiratory function. By use of this system for quantification of the extent and complications of the ARDS condition the specific ventilatory or cardiodynamic therapy can be tailored to meet the patient's physiologic needs. Techniques for optimization of conventional ventilator therapy are described and its application to the specific instances of combined high frequency ventilation or differential lung ventilation are presented. The clinical experience with this unit in a major trauma center suggests that quantitative analysis of an individual patients' respiratory dysfunction permits a precise, accurate and more effective approach to determining corrective therapy in ARDS.
Int J Clin Monit Comput 1984
PMID:Computer-based evaluation of cardiopulmonary function for the optimization of ventilatory therapy in the adult respiratory distress syndrome. 654 30

To determine netilmicin pharmacokinetic parameters and to evaluate the use of a one-compartment pharmacokinetic model, 32 patients receiving netilmicin for suspected gram-negative sepsis were enrolled in our study protocol. Dose and dosage interval for each patient were determined by one-compartment pharmacokinetic analysis of six postinfusion netilmicin serum samples (0.16, 0.33, 0.5, 1, 2, and 3 h) measured by radioimmunoassay. In patients with a normal serum creatinine, mean (+/- SD) half-life and distribution volume were 1.9 +/- 1.1 h and 0.2 +/- 0.8 L/kg, respectively. The average daily dose and mean days of therapy were 5.1 +/- 1.9 mg/kg/day for 7.3 +/- 2.8 days. Serum creatinine changes of greater than 0.5 mg% occurred in 2 of 28 (7%) patients. Substantial variability in half-life and distribution volume occurred in patients. Initial dosages of 5-7 mg/kg/day in divided dosages seem appropriate for adult patients with normal renal function. Monitoring of serum levels and adjustment of dose and dosage interval are necessary to maintain therapeutic antibiotic concentrations. As with other aminoglycosides, the one-compartment pharmacokinetic model proved to be an acceptable method for measuring netilmicin pharmacokinetic parameters and individualizing therapy.
Ther Drug Monit 1983
PMID:Clinical use of a one-compartment model for determining netilmicin pharmacokinetic parameters and dosage recommendations. 663 53

The chemistry, mode of action, antimicrobial activity, pharmacokinetics, and therapeutic efficacy of doxycycline are reviewed. Doxycycline displays excellent activity against gram-positive and gram-negative aerobic and anaerobic pathogens. The oral absorption of doxycycline is rapid and virtually complete and is not significantly decreased by food. Moreover, serum concentrations of doxycycline following oral and intravenous (i.v.) administration are comparable. Because of the prolonged half-life of doxycycline, once daily administration is possible. Tissue penetration of doxycycline is excellent. Levels within the therapeutic range have been found in most organs and tissues, including kidney, lung, gallbladder, prostate, intestinal tract, myocardium, sinus secretions, tonsil, aqueous humor, and female reproductive tissue. Doxycycline does not accumulate in patients with renal insufficiency and is not removed from the blood to any great extent during hemodialysis. Extensive clinical investigation has shown doxycycline to be highly effective in infections of the respiratory tract, including atypical pneumonias; skin and soft tissue; genitourinary infection including gonorrhea, syphilis, nonspecific urethritis, and prostatitis; intraabdominal infection due to trauma, sepsis, or surgery; and cholera. Evidence also suggests that doxycycline will prove effective in the treatment of Legionnaires' disease. In addition, placebo-controlled clinical trials suggest doxycycline is effective in the prevention of traveler's diarrhea.
Ther Drug Monit 1982
PMID:Doxycycline. 704 45

The prognostic value of a dynamic liver-function test, based on the hepatic conversion of lidocaine to monoethylglycinexylidide (MEGX), in predicting multiple organ failure (MOF) was prospectively investigated in 28 critically ill patients after multiple trauma. The MEGX test and conventional static liver tests (bilirubin, aspartate aminotransferase, glutamate dehydrogenase, and factor V) were performed on days 1, 3, 5, and 7 after trauma. Patients were classified by a modified MOF score into a group without (n = 18) and a group with the MOF syndrome (n = 10). One patient who developed MOF on the basis of a bacterial septicemia was excluded from the general evaluation. No significant differences were observed in the MEGX values of the two groups on day 1. All patients who subsequently developed MOF, however, displayed a sharp decrease in their MEGX values between days 1 and 3. Analysis of the data using receiver operating characteristic (ROC) curves revealed that the results of the MEGX test on day 3 provided the greatest discriminating power between patients with and without subsequent MOF. A cut-off MEGX value of 30 micrograms/L on day 3 was associated with a prognostic sensitivity of 89% and a prognostic specificity of 94%.
Ther Drug Monit 1995 Apr
PMID:Monoethylglycinexylidide as an early predictor of posttraumatic multiple organ failure. 762 99


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