Lung water quantitation by nuclear magnetic resonance imaging.

Nuclear magnetic resonance imaging was used to determine quantitatively the water distribution of saline-filled and normal rat lungs in both isolated lung and in situ preparations. Regional lung edema was easily detected. Studies of an isolated lung fragment indicate an accuracy of better than 1 percent and images of H2O/D2O phantoms indicate an average error of 2.7 percent.

Reasons for declining computerized insulin protocol recommendations: application of a framework.

Clinical decision support systems (CDS) can interpret detailed treatment protocols for ICU care providers. In open-loop systems, clinicians can decline protocol recommendations. We capture their reasons for declining as part of ongoing, iterative protocol validation and refinement processes. Even though our protocol was well-accepted by clinicians overall, noncompliance patterns revealed potential protocol improvement targets, and suggested ways to reduce barriers impeding software use. We applied Rita Kukafka and colleagues' (2003) IT implementation framework to identify and categorize reasons documented by ICU nurses when declining recommendations from an insulin-titration protocol. Two methods were used to operationalize the framework: reasons for declining recommendations from actual software use, and a nurse questionnaire. Applying the framework exposed limitations of our data sources, and suggested ways to address those limitations; and facilitated our analyses and interpretations.

A frame-based representation for a bedside ventilator weaning protocol.

We describe the use of a frame-based knowledge representation to construct an adequately-explicit bedside clinical decision support application for ventilator weaning. The application consists of a data entry form, a knowledge base, an inference engine, and a patient database. The knowledge base contains database queries, a data dictionary, and decision frames. A frame consists of a title, a list of findings necessary to make a decision or carry out an action, and a logic or mathematical statement to determine its output. Frames for knowledge representation are advantageous because they can be created, visualized, and conceptualized as self-contained entities that correspond to accepted medical constructs. They facilitate knowledge engineering and provide understandable explanations of protocol outputs for clinicians. Our frames are elements of a hierarchical decision process. In addition to running diagnostic and therapeutic logic, frames can run database queries, make changes to the user interface, and modify computer variables.

Variable estimates of serum growth hormone concentrations by different radioassay systems.

Many different assays are being used to measure serum GH concentrations in children with disorders of growth. We assessed four readily available methods to determine the comparability of the immunopotency estimates: standard double antibody RIA with pituitary standards from the National Hormone and Pituitary Program (assay 1) and from a commercial source (assay 2), a double antibody RIA with serum standards (assay 4), and a commercial immunoradiometric assay (assay 3). There was a high degree of relative correlation between assays (r = 0.95-0.98), but absolute potency estimates differed. Assays 1 and 2 were almost identical. Assay 3 yielded serum GH levels about 65% those of assay 1 or 2 and 80% those of assay 4. Assay 4 gave intermediate values between the low readings in assay 3 and higher values in assay 1 and 2. We conclude that substantial variation occurs in potency estimates in different GH assays. Such differences can affect the interpretation of many GH provocative and sampling studies.

Absence of nonclassical congenital adrenal hyperplasia in patients with precocious adrenarche.

We studied 31 patients (28 girls and 3 boys), ranging in age from 3.2-7.9 yr, with precocious adrenarche defined by the presence of early sexual hair development, no signs of virilization, and bone age within +3 SD of the mean for chronological age. To determine if this symptom complex stemmed from any form of nonclassical (late-onset) congenital adrenal hyperplasia, an ACTH stimulation test was performed on each patient using a standard 0.25-mg dose of Cortrosyn, given as an iv bolus. Twelve pubertal children (7 girls and 5 boys) and 18 prepubertal children (11 girls and 7 boys) served as normal controls. Baseline and stimulated 17-hydroxypregnenolone (17-OHPreg), 17-hydroxyprogesterone, (17-OHP), 11-deoxycortisol, dehydroepiandrosterone, androstenedione, testosterone, and cortisol levels were measured. Using published nomogram standards for serum 17-OHP response to ACTH, no child with precocious adrenarche was diagnosed as having nonclassical 21-hydroxylase deficiency. Eight girls, however, had a stimulated 17-OHP value that exceeded the mean response for pubertal and prepubertal controls by more than +2 SD [range, 295-670 ng/dL (8.94-20.3 nmol/L)]. Stimulated 11-deoxycortisol values [less than 400 ng/dL (11.6 nmol/L)] ruled out any cases of nonclassical 11 beta-hydroxylase deficiency. No patient had nonclassical 3 beta-hydroxysteroid dehydrogenase deficiency, as defined by both the stimulated 17-OHPreg and the 17-OHPreg/17-OHP ratio to be more than +2 SD above the mean for pubertal children [1354 ng/dL (41.0 nmol/L) and 10.4, respectively]. In conclusion, we could not provide any biochemical evidence for nonclassical congenital adrenal hyperplasia in a large group of children with precocious adrenarche.

Cardiovascular alterations in the adult respiratory distress syndrome.

We reviewed the hemodynamic data of 27 patients with severe adult respiratory distress syndrome (ARDS) and found significant elevations in heart rate, pulmonary artery pressure, and pulmonary vascular resistance and depressions of stroke index and left ventricular stroke work index. Altered left ventricular performance was suggested by a left ventricular stroke work index lower than expected for the level of wedge pressure in 19 patients and decreased slopes in nine of 11 ventricular function curves. Hemodynamic values in a subgroup receiving 0 to 5 cm H2O of positive end expiratory pressure (PEEP) were similar to those in the overall group (mean PEEP 12.5 +/- 7.9 cm H2O). Improvement in pulmonary and systemic hemodynamics occurred in survivors. Eight of 11 patients who underwent postmortem examination had cardiac abnormalities. The findings in this study suggest that changes in cardiovascular performance commonly occur in severe ARDS and that several mechanisms may contribute to the alterations.

Retinal blood flow following a tyramine-induced increase in blood pressure.

The effect of increasing systemic blood pressure on retinal blood flow was investigated in anaesthetised miniature pigs. Blood pressure was increased by the infusion of the sympathomimetic amine, tyramine. Volume flow was determined from axial erythrocyte velocity, measured by laser Doppler velocimetry, and vessel diameter, measured from monochromatic retinal photographs. Measurements were taken when mean arterial pressures were elevated by a mean of 22 +/- 3% and 50 +/- 8% above resting values, which represented increases of 31 +/- 2% and 74 +/- 16% in ocular perfusion pressures. Retinal blood flow increased by 8.5 +/- 8% at the lower infusion rate and by 57 +/- 19% at the higher infusion rate. We conclude that tyramine infusion is a suitable method for the study of retinal autoregulation and that the upper limit of retinal autoregulation in miniature pigs lies between 22-50% above resting mean arterial pressure.

Increased survival of ARDS patients with severe hypoxemia (ECMO criteria).

The adult respiratory distress syndrome (ARDS) is a form of diffuse lung injury associated with multiple risk factors. Patients with severe hypoxemia who meet blood gas criteria defined by the extracorporeal membrane oxygenation trial (ECMO) of 1974 to 1977 have a reported survival of 11 percent. The reported survival has remained unchanged for 15 years despite numerous technologic advances. We prospectively studied ARDS patients who met ECMO blood gas criteria. One hundred seventy-eight ARDS patients were prospectively screened over a 30-month period. Fifty-one of these patients met ECMO blood gas criteria and 23 (45 percent) survived (p less than 0.001 vs ECMO trial). No obvious differences in etiology, APACHE II score, organ system failure, or the incidence of sepsis was found between survivors and nonsurvivors. We conclude that survival of ARDS patients who met ECMO blood gas criteria in our institution is higher than that previously reported from both other centers and our own hospital.

A prospective study of acute hypoxic respiratory failure.

A prospective study of acute hypoxic respiratory failure was carried out by nine centers in a collaborative NIH study from 1 September 1975 to 1 March 1977. Serious hypoxic respiratory failure was defined in 713 patients by the presence of (1) endotracheal intubation and positive airway pressure for at least 24 hours, and (2) the administration of at least 50 percent oxygen. The 490 patients between 12 to 65 years of age had a mortality of 61 percent. Mortality increased with increasing organ failure: one organ system failure (lung only) 40 percent; two, 54 percent; three, 72 percent; four, 84 percent, five, 100 percent. Only 103 patients died with isolated lung failure, whereas 353 died of a combination of lung and other organ failures. Both the overall mortality (66 percent) and the mortality of those with only isolated lung failure (40 percent) were much higher than anticipated for the selection criteria.

Open lung biopsy does not correlate with pulmonary function after the adult respiratory distress syndrome.

Abnormalities of pulmonary function occur following the adult respiratory distress syndrome (ARDS). To determine if open lung biopsy (OLB) during ARDS predicts late pulmonary function abnormalities, we examined nine survivors of ARDS who had OLB during ARDS. Open lung biopsy was performed within two weeks of the diagnosis of ARDS, and the following were scored by a pulmonary pathologist as to extent and severity: hyaline membranes (HM), interstitial fibrosis (IF), air space organization (AO), interstitial cellularity (IC), and type 2 cell proliferation (T2C). Pulmonary function tests performed at least one year after ARDS were also used for analysis. Percent predicted Dco, TLC, DL/VA, and FVC were regressed against extent, severity, and combined scores. No significant correlation was found despite impressive histologic abnormalities. These data suggest that the severity and extent of HM, IF, AO, T2C, or IC do not correlate with lung function following ARDS.

Increased mortality of older patients with acute respiratory distress syndrome.

OBJECTIVE: To examine the relationship between age and mortality in ARDS patients and evaluate the importance of factors that increase the mortality of older ARDS patients. DESIGN: Prospective inception cohort study. SETTING: Community-based referral hospital. PATIENTS: Two hundred fifty-six ARDS patients identified from May 1987 to December 1990. ARDS was defined by the following: (1) PaO2/PAO2 < or = 0.2; (2) pulmonary capillary wedge pressure < or = 15 mm Hg; (3) total static thoracic compliance < or = 50 mL/cm H2O; (4) bilateral infiltrates on chest radiograph; and (5) an appropriate clinical setting for ARDS. MAIN OUTCOME MEASURES: Comparison of organ failure, incidence of sepsis, patient demographics, arterial oxygenation, and level of support in those 55 years and younger and those older than 55 years of age. Withdrawal of support in patients who died. RESULTS: Seventy-two of 112 patients older than 55 years (64%) died vs 65 of 144 patients 55 years and younger (45%) (p = 0.002). Examination of patient groups using age identified older than 55 years as a "cutpoint" above which mortality was greater (p = 0.002). Older nonsurvivors did not differ from nonsurvivors 55 years or younger with respect to gender, smoking history, ARDS risk factors, ARDS identifying characteristics, APACHE II (acute physiology and chronic health evaluation), number of organ failures, or the incidence of sepsis. In the 48 h prior to death, nonsurvivors 55 years and younger had more organ failure (3.4 +/- 0.2 vs 2.8 +/- 0.2; p = 0.03), higher fraction of inspired oxygen (0.82 +/- 0.03 vs 0.68 +/- 0.03; p = 0.008), and higher positive end-expiratory pressure levels (13 +/- 1 vs 8 +/- 1; p = 0.001) than older nonsurvivors. Despite more severe expression of disease, only 32 (50%) nonsurvivors 55 years and younger had support withdrawn. Significantly more nonsurvivors older than 55 years (73%) had support withdrawn (p = 0.009). Even in the absence of chronic disease states, withdrawal was more likely for patients older than 55 years (21/51) than in those 55 years and younger (3/32; p < 0.001). CONCLUSIONS: Mortality is significantly higher for patients with ARDS older than 55 years. Decisions to withdraw support are made more often in ARDS patients older than 55 years. These data suggest that age bias may influence decisions to withdraw support.

A successful computerized protocol for clinical management of pressure control inverse ratio ventilation in ARDS patients.

We have developed a computerized protocol that provides a systematic approach for management of pressure control-inverse ratio ventilation (PCIRV). The protocols were used for 1,466 h in ten around-the-clock PCIRV evaluations on seven patients with severe adult respiratory distress syndrome (ARDS). Patient therapy was controlled by protocol 95 percent of the time (1,396 of 1,466 h) and 90 percent of the protocol instructions (1,937 of 2,158) were followed by the clinical staff. Of the 221 protocol instructions, 88 (39 percent) not followed were due to invalid PEEPi measurements. Compared with preceding values during CPPV, the expired minute ventilation was reduced by 27 percent during PCIRV while maintaining a pH that was not clinically different (mean difference in pH = 0.02). There was no difference in the PaO2, PEEPi, or the FIO2 between PCIRV and CPPV. The PEEP setting was reduced by 33 percent from 9 +/- 0.05 to 6 +/- 0.6 and the I:E ratio increased from 0.64 +/- 0.04 to 2.3 +/- 0.10. Peak airway pressure was reduced by 24 percent (from 59 +/- 1.5 to 45 +/- 0.6) and mean airway pressure increased by 27 percent (from 22 +/- 0.8 to 28 +/- 0.6) in PCIRV. Right atrial and pulmonary artery pressures were higher and cardiac output lower in PCIRV but blood pressure was unchanged. The success of this protocol has demonstrated the feasibility of using PEEPi as a primary control variable for oxygenation. This computerized PCIRV protocol should make the future use of PCIRV less mystifying, simpler, and more systematic.

Asymmetric spin echo sequences. A simple new method for obtaining NMR 1H spectral images.

The nuclear magnetic resonance (NMR) signal decay produced by reversible tissue-induced dephasing of the magnetization components in the transverse plane (reversible tissue-induced dephasing) was measured and expressed as a function of a new transverse relaxation time T'2 (T2 prime) for samples of rat liver, retroperitoneal fat, inflated lung, and corn oil. Simple exponentials did not adequately describe the observed NMR signal decay. Inflated lung demonstrated the most rapid signal decay (T'2 = 4.8 ms) followed by retroperitoneal fat (T'2 = 16 ms). No reversible tissue-induced dephasing was observed in liver (T'2 immeasurably long). In tissues which contain both fat and water, the chemically shifted 1H resonance peaks from -OH and -CH-are in phase with symmetric spin echo sequences but out of phase with asymmetric sequences. The interference of these two peaks produces a beat pattern with asymmetric sequences. Subtraction images obtained from paired symmetric- and asymmetric-sequence images accurately (r = .96) reflect T'2 and can be used to indicate the presence of fat. In vivo subtraction images of ethionine-induced fatty rat livers were significantly different from similar in vivo images of normal rat livers (P less than .0005). Since for each pixel of a subtraction image, the magnitude of the difference signal should be approximately proportional to the ratio of hydroxyl and alkyl protons, this simple spin echo sequence modification may obviate the need for more time-consuming 3-dimensional Fourier transform proton chemical shift images.

Alveolar air-tissue interface and nuclear magnetic resonance behavior of lung.

Inflated lungs are characterized by a short nuclear magnetic resonance (NMR) free induction decay (rapid disappearance of NMR signal), likely due to internal (tissue-induced) magnetic field inhomogeneity produced by the alveolar air-tissue interface. This phenomenon can also be detected using temporally symmetric and asymmetric NMR spin-echo sequences; these sequences generate a pair of NMR images from which a difference signal (delta) is obtained (reflecting the signal from lung water experiencing the air-tissue interface effect). We measured delta in normal excised rat lungs at inflation pressures of 0-30 cmH2O for asymmetry times (a) of 1-6 ms. Delta was low in degassed lungs and increased markedly with alveolar opening when measured at a = 6 ms (delta 6 ms); delta 6 ms varied little during the rest of the inflation-deflation cycle. Delta 1 ms (a = 1 ms) did not vary significantly on inflation and deflation. Measurements of delta at a = 3 and 5 ms generally lay between those of delta 1 ms and delta 6 ms. These findings, which are consistent with theoretical predictions, suggest that measurements of delta at appropriate asymmetry times are particularly sensitive to alveolar opening and may provide a means of distinguishing alveolar recruitment from alveolar distension in the pressure-volume behavior of the lung.

Lung water measurement by nuclear magnetic resonance: correlation with morphometry.

Estimates of lung water content obtained from nuclear magnetic resonance (NMR) and morphometric and gravimetric measurements were compared in normal and experimentally injured rats. Average lung water density (rho H2O) was measured by an NMR technique in excised unperfused rat lungs (20 normal lungs and 12 lungs with oleic acid-induced edema) at 0 (full passive deflation) and 30 cmH2O lung inflation pressure and in vivo (4 normal rats and 8 rats with lung injury induced by oleic acid or rapid saline infusion). The rho H2O values were compared with morphometric measurements of lung tissue volume density (Vv) obtained from the same lungs fixed at corresponding liquid-instillation pressures. A close correlation was observed between rho H2O and Vv in normal and injured excised lungs [correlation coefficient (r) = 0.910, P < 0.01]. In vivo rho H2O was also closely correlated with Vv (r = 0.897, P < 0.01). The correlation coefficients between rho H2O and gravimetric lung water content (LWGr) were lower in the excised lung group (r = 0.663 and 0.692, respectively, for rho H2O at 0 and 30 cmH2O lung inflation pressure, P < 0.01) than in the in vivo study (r = 0.857, P < 0.01). Our results indicate that NMR techniques, which are noninvasive and nondestructive, provide reliable estimates of lung water density and that the influence of lung inflation on rho H2O is important (compared with the effect of lung water accumulation in lung injury) only in the presence of deliberately induced very large variations in the lung inflation level.

A new nuclear magnetic resonance property of lung.

Inflated lung has a nuclear magnetic resonance (NMR) free-induction decay (FID) which is short compared with that of collapsed lung and those of other body tissues. An almost identically short FID is obtained from a slurry of 5-micron alumina particles in water. Interfaces between air and water in lung and between alumina and water in the slurry appear to be the source of spatial internal magnetic inhomogeneities which produce NMR line broadening and the short FID. Paired images that included lung, taken with paired symmetric and asymmetric NMR spin-echo sequences, permit the generation of an image, by subtraction, of the lung isolated from surrounding tissue. These new lung images are neither proton density, T1 (spin-lattice relaxation time), nor T2 (spin-spin relaxation time) images. They complement current NMR images and provide information about regional lung inflation. This previously unrecognized NMR property of lung tissue has potential application in NMR imaging, in quantitative determination of lung water and its distribution, and in the quantitation of regional lung inflation.

Decision support and safety of clinical environments.

Safety in the clinical environment is based on structures that reduce the probability of harm, on evidence that enhances the likelihood of actions that increase favourable outcomes, and on explicit directions that lead to decisions to implement the actions dictated by this evidence. A clinical decision error rate of only 1% threatens patient safety at a distressing frequency. Explicit computerised decision support tools standardise clinical decision making and lead different clinicians to the same set of diagnostic or therapeutic instructions. They have favourable impacts on patient outcome. Simple computerised algorithms that generate reminders, alerts, or other information, and protocols that incorporate more complex rules reduce the clinical decision error rate. Decision support tools are not new; it is the new attributes of explicit computerised decision support tools that deserve identification. When explicit computerised protocols are driven by patient data, the protocol output (instructions) is patient specific, thus preserving individualized treatment while standardising clinical decisions. The expected decrease in variation and increase in compliance with evidence-based recommendations should decrease the error rate and enhance patient safety.

Computerized protocols and bedside decision support.

Many clinicians are concerned that protocol supported care will become rote or "cookbook" care and will be generated without attention to the specific and changing needs of the individual critically ill patient. This article addresses that concern. In addition, the author discusses the potential advantages that this decision-support approach, with bedside computerized protocols, brings to the healthcare delivery system, and what contributions to clinical care and to clinical research might be anticipated from its widespread application.

Granulocyte aggregation in adult respiratory distress syndrome (ARDS)--serial histologic and physiologic observations.

Although a number of studies have suggested that granulocyte sequestration is an important pathophysiologic event in ARDS, histologic evidence of aggregated granulocytes in the pulmonary microvasculature is limited, and serial histologic data have not been reported with physiologic measurements. We report a patient with ARDS who demonstrated microvascular granulocyte aggregation and lung edema in sections of a lung biopsy obtained seven days after the onset of symptoms. Pulmonary vascular resistance and pulmonary capillary wedge pressure were normal immediately before the biopsy. A second biopsy performed 12 days later showed decreased lung edema and no evidence of intravascular leukostasis. This case provides histologic support for the hypothesis that granulocyte aggregates contribute to pulmonary edema associated with ARDS.

Cost-benefit considerations in managing oxygenation failure.

The evaluation of new therapy poses a formidable challenge in intensive care medicine. When therapy evaluation cannot be double-blinded, as in the evaluation of extracorporeal support, the problem becomes more difficult. The result of the extracorporeal clinical trial, like that of the ECMO trial in the 1970s, is a potent reminder of the importance of concurrent controls in such evaluations. We should view with caution ethical objections to controlled trials of therapies that are not supported by credible data. A stronger ethical argument may frequently be mounted in favor of a randomized, controlled clinical trial. This is particularly pertinent in the high-technology ICU environment in which information overload is intense. The establishment of ICU human laboratories should enable the medical community to make much needed progress and help us identify the useful elements in our therapeutic armamentarium.