Assessment of fetal lung maturity. Practice parameter.

Despite the development of artificial surfactant and advances in respiratory support, respiratory distress syndrome (RDS) remains a major clinical concern. The relatively low prevalence of RDS requires test methods with very high diagnostic sensitivity and specificity for fetal lung maturity (FLM). Such methods often require sophisticated instrumentation, skilled staff, and long analytic times. This practice parameter discusses the usefulness of widely available methods and reaches several conclusions: (1) A satisfactory specimen of amniotic fluid is essential for effective laboratory assessment of FLM. (2) No test is immune from analytic interferences. (3) The lecithin/sphingomyelin (L/S) ratio or phosphatidylglycerol (PG) by thin-layer chromatography are unnecessary as obligatory panel components. (4) Either fluorescence polarization or lamellar body number density is an acceptable initial screening test. If maturity is indicated, no further testing is generally necessary. (5) If the result of the initial test in no. 4 is below but near the maturity criterion, the second rapid test usually can offer resolution; if the result is still immature, a third rapid test can be added (PG by Amniostat-FLM). (6) In the setting of poorly controlled diabetes, PG assessment by Amniostat-FLM should be performed to rule out false maturity predictions by the other rapid tests. Nevertheless, RDS will not develop in most fetuses in whom PG is not detected. (7) Clinical judgment remains the single most important criterion for fetal delivery.

Evaluation of lamellar body number density as the initial assessment in a fetal lung maturity test cascade.

The objective of this study was to assess the sensitivity and specificity of lamellar body number density in the prenatal prediction of the respiratory distress syndrome. Seventy consecutive amniotic fluid specimens obtained by amniocentesis within 72 hours of delivery were assessed for lamellar body number density, optical absorbance at 650 nm, lecithin/sphingomyelin ratio and phosphatidylglycerol. A maturity criterion of > or = 46,000/microL for lamellar body number density yielded values for diagnostic sensitivity of 100% (7/7), specificity of 89% (49/55), positive predictive value of 54% (7/13) and negative predictive value of 100% (49/49). These values were also determined for the other analytes, with results similar to those reported elsewhere. Lamellar body number density is an effective and inexpensive first test for the rapid identification of the fetus at high risk for the respiratory distress syndrome. A cascade approach, using lamellar body number density as the first test and optical absorbance at 650 nm as the second test, improves the predictive value as compared to any single test of fetal lung maturity.

Assessment of fetal lung maturity by laboratory methods.

I have reviewed many of the methods available for the assessment of fetal lung maturity. The difficulty of using diagnostic tests for diseases of low prevalence has been discussed. By reviewing the nature of the amniotic fluid surfactant material, and some of the principles underlying analytical methods, the bases of some of the recurring methodologic problems have been pointed out. It is concluded that a number of reasonably straightforward tests will provide information of essentially the same utility as more costly, difficult, and time-consuming assays commonly employed.

The laboratory assessment of fetal lung maturity.

The assessment of fetal lung maturity by laboratory methods is reviewed, and the utility of the various approaches in the prediction of respiratory distress syndrome is discussed. Because of the relatively low prevalence of respiratory distress syndrome, methods with exceptionally high diagnostic sensitivity and specificity are required; such methods are rarely available for any diagnostic evaluation, and the methods with the greatest clinical acceptance in assessing fetal lung maturity have been those which require the most personnel time and skill. The consequences of laboratory testing in the environment of low prevalence diseases is discussed. Because of the clinical implications of an erroneous determination of fetal lung maturity, particularly in the case of incorrectly assessing the fetal lungs to be mature, a strong emotional overlay exists for accepting only the "reference method" or "gold standard" in this determination. This review briefly discusses the utility of commonly used methods in the context of the physical and chemical concepts. By reviewing the underlying principles of the methods, the origins of some of the frequently observed problems in this field are revealed. The emphasis is on practical application and issues of use both to clinician and laboratory in approaching this controversial and difficult area of assessment. It is demonstrated that there are several reasonably straightforward approaches which will provide appropriate clinical information more quickly, easily, and inexpensively than the methods generally requested.

Early absorption of enteral ranitidine after major laparotomy.

Thirty-six patients were studied following abdominal aortic surgery to determine if a commonly used medication could be absorbed from the gastrointestinal (GI) tract in the early postoperative period. Patients were randomized into two groups: Group I received ranitidine elixir 3 mg/kg via nasogastric tube every 12 hours; Group II received intravenous (IV) ranitidine 1 mg/kg every 8 hours. Ranitidine serum levels were measured with high performance liquid chromatography 1 hour after administration of the first three doses. Gastric pH was measured every 4 hours. It was found that serum ranitidine levels generally regarded as clinically effective were achieved in both groups. Although the levels were significantly higher following intravenous (IV) administration (Group II), there were no differences in average gastric pH. The authors conclude that within 24 hours of aortic surgery enterally administered ranitidine is effectively absorbed and provides prophylaxis equivalent to IV administration of the drug at lower cost. Other medications might be deliverable via the GI tract in the early postoperative period.

Dissolution of peripheral arterial thrombi by ultrasound.

BACKGROUND: We have previously shown that continuous-wave ultrasound can rapidly dissolve human thrombi in vitro, with 99% of all residual particles measuring less than 10 microns in diameter. To assess the effects of pulsed-wave ultrasound energy on whole blood clots, 1) in vitro studies were preformed to assess precisely the rates of clot disruption and to quantify particulate size, and 2) in vivo studies were performed to assess the efficacy and safety of catheter-delivered ultrasound for intra-arterial thrombus dissolution. METHODS AND RESULTS: In vitro, we studied 50 samples of human whole blood clots and using an 89-cm-long wire probe, applied pulse-wave energies from 8 to 23 W. The corresponding peak-to-peak tip displacement range was 63.5 - 102 microns. We studied arterial thrombosis in vivo in 21 canine superficial femoral arteries. To produce an acute thrombosis, 200 units of thrombin followed by 2 ml of 72-hour-old autologous clot were injected into a 5-7-cm segment of femoral artery and left to coagulate for 2 hours. Ultrasound energy was intermittently applied at a frequency of 20 kHz with a prototype ultrasound wire ensheathed in a catheter and directed to clots by fluoroscopy. In nine cases, angioscopic guidance was used to put the probe into direct contact with the intra-arterial thromboses. In vitro clot dissolution times were inversely related to the ultrasound power output (r = 0.95). All in vivo canine thromboses were disrupted in 4 minutes or less. All successful recanalizations were confirmed by angiography and in nine cases by angioscopy as well. Angioscopy demonstrated that probe activation caused rapid clot disruption. Histological studies of the vessels showed no evidence of thermal or cavitation injury, occlusive distal embolization, or perforation. CONCLUSIONS: Our findings in this experimental canine model suggest that ultrasound clot dissolution has the potential to be an effective and safe alternative to current treatment modalities for peripheral arterial thrombosis.

Three rapid immunoassays for the determination of creatine kinase MB: an analytical, clinical, and interpretive evaluation.

We present analytical and clinical studies of three commercial immunoassays for the determination of the creatine kinase MB isoenzyme (CK-MB). All methods are compared with the presently-accepted reference method, agarose gel electrophoresis. We find that each of the immunoassay methods offers diagnostic sensitivity and specificity similar to those of electrophoresis, while none experiences detectable interference from high concentrations of the creatine kinase BB isoenzyme (CK-BB) or the so-called "atypical" bands. The presence of atypical bands can cause electrophoresis to yield inaccurate quantification or even misidentification of CK-MB. Because the immunoassay approaches are more rapid than electrophoresis and require less technical expertise, it is possible to evaluate patients in a more timely and cost-effective manner. Further, since immunoassay results can be available in approximately 1/2 hour, rapid real-time decisions can be made regarding the desirability of initiating or continuing such valuable but dangerous procedures as thrombolytic therapy.

Ultrasonic clot disruption: an in vitro study.

We studied in vitro the efficacy of ultrasound in human blood clot disruption, as well as the effects of clot age, wire probe length, and streptokinase on the outcome. The study included sizing the resulting particulate debris. Clot age (1 to 7 days) had no effect on the time required for disruption. Three groups of 1-day-old clots (n = 10 for each) were exposed to the same ultrasonic power source via probes of different lengths. The time required for clot disruption varied approximately as the square of the length for probes of 31, 56, and 105 cm, but was less than 3 minutes even for the longest probe employed. Disrupted whole-blood clot as well as cell-free fibrin clot solutions were analyzed for particulates by the resistive-pulse technique (size range: 2.5 to 80 microns). Debris as large as 80 microns were seen after disruption of whole blood clots, while cell-free fibrin clots contributed little above 40 microns. In all size ranges, whole blood clots produced two orders of magnitude more particulates than cell-free fibrin clots. Addition of streptokinase (7500 U/mL) had little effect on the size distribution of debris, with 99% of all particulates being smaller than 10 microns. D-dimer analysis was performed on the dissolved cell-free fibrin clots with and without streptokinase. While the former had analytically higher D-dimer concentrations than the latter (from eight- to 16-fold), the levels in both cases would be below detectability if measured in vivo. Hence the present study supports the concept that ultrasound can be employed to disrupt human blood clots by mechanisms (mechanical and cavitational) other than fibrinolysis.

Decision support alerts for clinical laboratory and blood gas data.

We have designed and implemented a computerized Intensive Care Unit (ICU) decision support alerting system which analyzes all incoming laboratory and blood gas data for critically abnormal values and trends. A computerized patient data management system (HP 78709A PDMS, Hewlett-Packard Co., Waltham, MA) serving 20 Surgical ICU beds is networked to a Clinical Laboratory Information System and a blood gas computer system. The ALERTS subsystem operates on the PDMS as an automatic program triggered by the receipt of fresh laboratory data. Three types of ALERTS are detected: (1) high and low critical values, (2) calculation-adjusted critical values, and (3) critical trends. Once detected, a specific ALERT message is displayed at the bottom of the patient's bedside PDMS terminal and at the central station. Over an eight month period a total of 1,515 ALERTS were detected from amongst approximately 115,000 laboratory data results transmitted to the Surgical Intensive Care Unit (SICU). Slightly over half of all ALERTS were caused by critical blood gas values. ALERTS were found to be a sensitive indicator of severity of illness: patients with one or more ALERTS suffered an ICU mortality of 9.52%, compared to 0% mortality in patients with no ALERTS. We conclude that automated laboratory data ALERTS represent a valuable decision support tool for the management of high risk ICU patients.

Absence of hepatitis B surface antigenemia after vaccination.

Vaccination against hepatitis B is readily available and provides safe and effective immunization for individuals at increased risk for this disease. However, since the available vaccines employ a protein consisting of hepatitis B surface antigen, the question has arisen whether a detectable surface antigenemia might occur in recently vaccinated individuals. Employing two current immunoassays for hepatitis B surface antigen, we could not detect this marker in individuals either 1 hour or 24 hours after vaccination. We therefore conclude that the presence of surface antigen in the blood cannot be attributed to recent vaccination.

Characterization of amniotic fluid lamellar bodies by resistive-pulse counting: relationship to measures of fetal lung maturity.

Resistive-pulse counting studies of amniotic fluid lamellar bodies are presented and demonstrate a strong concordance with the predictions of accepted measures of fetal lung maturity. Uncentrifuged as well as centrifuged specimens could be evaluated, because cells and debris are rejected electronically. The technique is not affected by bilirubin or debris of lysed whole blood, and only mildly by meconium. Lamellar body number density and mean lamellar body volume were determined for 161 uncentrifuged and 241 centrifuged specimens. Number density maturity criteria (40,000/microL and 26,000/microL, respectively) were shown to be highly concordant with established measures of fetal lung maturity; mean lamellar body volume did not extend this concordance. Since electronic cell counters are generally available 24 h per day and the approach requires neither centrifugation nor subjective interpretation and is rapid and inexpensive, it is proposed that determining lamellar body number density by resistive-pulse counting may be a useful initial screen for the assessment of fetal lung maturity.

The effect of hemolysis on creatine kinase determination.

Hemolysis can cause falsely elevated creatine kinase (CK) values when spectrophotometric methods of measurement are used. This apparent increase in CK is due to the red blood cell enzyme adenylate kinase. In an attempt to reduce this interference, most commercial CK kits employ adenosine monophosphate and/or diadenosine pentaphosphate as adenylate kinase inhibitors. To determine whether hemolyzed specimens should be accepted for testing, we measured the CK values of 26 serum samples, each with six different concentrations of added hemolysate. The results showed that hemolysis had an additive effect on CK, with an average increase in CK of approximately 10 U/L for every 1 g/L of hemoglobin. In most settings, this increase is not clinically significant. In the case of massive hemolysis, the hemoglobin concentration of the serum can be measured to correct the apparent CK value. The exclusion of hemolyzed specimens is unnecessary.

Determination of lamellar body size, number density, and concentration by differential light scattering from amniotic fluid: physical significance of A650.

A new method for characterizing amniotic fluid is presented. The difference in optical absorbance between amniotic fluid diluted with distilled water or glycerol is measured. This differential approach is shown to determine the total light scattered by the surfactant-containing lamellar bodies and not to be affected by interfering chromogens. The lamellar body size, number density, and concentration are in turn quantified from the wavelength dependence of the absorbance difference, which is shown to be accurately predicted by light-scattering theory in the domain of "anomalous diffraction." The concentration of the lamellar bodies is demonstrated to be directly related to the absorbance difference at 650 nm. A maturity criterion, based on that generally accepted for the direct measurement of absorbance at 650 nm (that is, A650 greater than or equal to 0.15), is determined for the differential approach. Hence, measurement of the absorbance difference at 650 nm can be used to assess amniotic fluid both for its optical absorbance and its lamellar body concentration.

Kinetics of bilirubin photodegradation with application to amniotic fluid.

By spectrophotometric methods we have studied the photodegradation of bilirubin in simple solution and in amniotic fluid and have found that: (1) the photodegradation process can be described by kinetics which are first-order in concentration and second-order in time; (2) the photodegradation products of bilirubin do not prevent the determination of the absorbance of the parent compound; (3) although the rate of the photodegradation process depends upon both the oxygen partial pressure and the irradiation intensity, the determination of the original bilirubin absorbance is independent of both of these parameters so long as they are constant over the period of photodegradation; (4) other chromagens in amniotic fluid (including hemoglobin and methemoglobin) experience little photodegradation in the time required to degrade bilirubin; (5) several absorbance measurements over a short (approximately five-minute) period of photodegradation are sufficient for the determination of the original bilirubin absorbance for the complete range of interest in amniotic fluid with an accuracy of about five percent.

The effect of succinate on the translational diffusion coefficient of aspartate transcarbamylase.

Employing a differential optical mixing spectrometer, we have determined that the translational diffusion coefficient (DT) of aspartate transcarbamylase (AT-Case) decreases by (4.1 plus or minus 0.6)% in the presence of succinate and carbamyl phosphate. This result, combined with the change in the sedimentation coefficient determined by Gerhart and Schachman (1968) and repeated by us in the present work indicates that ATCase experiences an increase in frictional coefficient of approximately 4% due to succinate and carbamyl phosphate, and that any change in the enzyme's partial specific volume (v) under these conditions is less than about 0.3%. We have also measured (DT)20,w for ATCase as (3.75 plus of minus 0.11) x 10-7 cm2/sec. Combining this with our measured value of s20,2-o for ATCase of (11.7 plus or minus 0.2) x 10-13 sec and the calculated value of v of 0.738 cm3/g (Rosenbusch and Weber, 1971), we have determined the molecular weight of ATCase as (2.9 plus of minus 0.1) x 10-5. We have also observed the ATCase dimer and find that at a dimer concentration of 0.6 mg/ml the value of s20,w for the dimer is 15.8 x 10-13 sec and that this value decreases by (4.0 plus or minus 0.5)% upon the addition of succinate and carbamyl phosphate, a behavior essentially identical with that of the monomer.