Sandra K. Hanneman

Design, Analysis, and Interpretation of Method-Comparison Studies

Clinicians often need to know whether a new method of measurement is equivalent to an established one already in clinical use. This article reviews the methodology of a method-comparison study to assist the clinician with the conduct and evaluation of such studies. Temperature data from 1 subject are used to illustrate the procedures. Although one would not make decisions on the basis of the findings from 1 subject, the large number of paired measurements in the data set permits its use for illustrative purposes. Currently available software eliminates the need for tedious statistical computation but does not reduce the burden of understanding the concepts underlying a method-comparison study and accurate interpretation of the findings.

Measuring Circadian Temperature Rhythm

Experimental control and mathematical techniques increase confidence that results of circadian temperature rhythm studies reflect true changes in the circadian timing system versus coupling with exogenous synchronizers. Masking effects represent confounding influences in studies that are concerned with the endogenous temperature rhythm. Because it is technically difficult to measure directly the behavior of the endogenous timing system, marker rhythms are used as proxy measures. However, in addition to entraining, the external environment exerts a direct masking effect on the monitored rhythm. Methods for measuring circadian temperature rhythm are reviewed in this article. Constant routine, forced desynchrony, and purification methods represent attempts, at an experimental or mathematical level, to remove masking effects and more accurately capture the endogenous circadian temperature rhythm. Exogenous factors have not been subjected to the same scrutiny as the endogenous features of circadian temperature rhythm. But it is the environmental context, the extent to which the endogenous features are adaptively modified by the field environment, that will ultimately determine the biological value of circadian temperature rhythm to the organism. Thus, nurse investigators are encouraged to use rigorous methods to study both endogenous circadian temperature rhythm and exogenous rhythms.

Multidimensional predictors of success or failure with early weaning from mechanical ventilation after cardiac surgery.

The purpose of this study was to determine the contributions of pulmonary mechanics, gas exchange, and hemodynamic function to prediction of success or failure with early weaning from mechanical ventilation after cardiac surgery. More than 40 physiologic measurements were determined on 162 patients at two time points in the early postoperative period: during full-support mechanical ventilation and during a trial of spontaneous ventilation. Discriminant analysis was used to analyze the differences between the success group (n = 134) and the failure group (n = 28) and to predict group membership of individual cases. A moderately strong relationship (canonical correlation = 0.733) was found between the groups and the discriminating variables. The discriminant function contained variables from all three dimensions of weaning criteria, with dimensions of hemodynamic function and pulmonary mechanics having greater import. The predictor set had a sensitivity of .98, specificity of .71, positive predictive value of .94, and negative predictive value of .87. Routine bedside measurements had a predictive performance equal or superior to variables previously studied.

Comparison of methods of temperature measurement in swine

The purpose of these experiments was to test the equivalence of pulmonary artery, urinary bladder, tympanic, rectal and femoral artery methods of temperature measurement in healthy and critically ill swine under clinical intensive care unit (ICU) conditions using a prospective, time series design. First, sensors were tested for error and sensitivity to change in temperature with a precision-controlled water bath and a laboratory-certified digital thermometer for temperatures 34-42°C. There was virtually no systematic (bias) or random (precision) error (<0.2°C). The bladder sensor had the slowest response time to change in temperature (105-120 s). Next, testing was done in an experimental porcine ICU in a non-profit research institution with four male, sedated, and mechanically ventilated domestic farm pigs. The in vivo experiments were conducted over periods of 41-168 h with temperatures measured every 1-5 s. The bladder, tympanic and rectal methods had unacceptable bias (≥0.5°C) and/or precision (≥0.2°C). Response time varied from 7 s with the femoral artery method to 280 s (4.7 min) with the tympanic method. We concluded that equivalence of the methods was insufficient for them to be used interchangeably in the porcine ICU. Intravascular monitoring of core body temperature produces optimal measurement of porcine temperature under varying conditions of physiological stability.

A pilot home study of temporal variations of symptoms in chronic obstructive lung disease.

The purposes of this pilot study are to describe the 24-hr patterns of dyspnea, fatigue, and peak expiratory flow rate (PEFR) in patients with chronic obstructive pulmonary disease (COPD) and examine their interrelationships. The repeated-measures design protocol involved 10 patients with moderate to severe COPD who self-assessed dyspnea, fatigue, and PEFR five times a day for 8 days. Circadian rhythms were documented by single cosinor analysis in 40% of the participants for dyspnea, 60% for fatigue, and 60% for PEFR. The 8-day, 24-hr means of dyspnea and fatigue were moderately correlated; 70% of the sample displayed significant correlations. The means of PEFR and both dyspnea and fatigue were weakly negatively correlated. The findings suggest that circadian rhythm in lung function may not be temporally coupled with the circadian rhythm in dyspnea and fatigue in all patients and that the mean self-perceived levels of dyspnea and fatigue are moderately related.

Cosinor Analysis for Temperature Time Series Data of Long Duration

The application of cosinor models to long time series requires special attention. With increasing length of the time series, the presence of noise and drifts in rhythm parameters from cycle to cycle lead to rapid deterioration of cosinor models. The sensitivity of amplitude and model-fit to the data length is demonstrated for body temperature data from ambulatory menstrual cycling and menopausal women and from ambulatory male swine. It follows that amplitude comparisons between studies cannot be made independent of consideration of the data length. Cosinor analysis may be carried out on serial-sections of the series for improved model-fit and for tracking changes in rhythm parameters. Noise and drift reduction can also be achieved by folding the series onto a single cycle, which leads to substantial gains in the model-fit but lowers the amplitude. Central values of model parameters are negligibly changed by consideration of the autoregressive nature of residuals.

Estimating Intra- and Inter-Assay Variability in Salivary Cortisol

Investigators commonly assess intra- and inter-assay coefficients of variation (CVs) to estimate the precision of salivary cortisol enzyme immunoassay (EIA). However, little guidance is available as to which samples to use for CV assessment. The purposes of this methodological study were to compare differences in intra- and inter-assay CVs (a) among controls, standards, and/or unknown samples; and (b) between fresh and previously frozen saliva. A total of 174 duplicates (controls = 58, standards = 48, and unknowns = 68) were tested. The unknowns were from 34 students; all student saliva was assayed as both fresh and frozen samples. All samples were assayed in duplicate, using a commercial salivary cortisol EIA kit, by the same technician with the same equipment. A priori criteria for intra- and inter-assay CV, respectively, were ≤ 4% and ≤ 7%, and a was .05 for CV differences. Mean intra-assay CVs for controls, standards, unknowns, and combined samples were ≤ 2.5%, and mean inter-assay CVs were ≤ 2.8%. Mean intra-assay CVs were 2.2% for fresh saliva and 1.5% for frozen samples. Comparisons showed no significant differences in intra- or inter-assay CV among controls, standards, and/or unknown samples. Inter-assay CV was significantly different between fresh and previously frozen saliva (p = .043), with fresh saliva CV higher than frozen; the difference was not meaningful because all evaluations showed minimal measurement error. In conclusion, results indicate that estimation of precision can be achieved by testing of controls, standards, or unknowns and with either fresh or frozen saliva in this population.

Cardiovascular impact of manual and automated turns in ICU

Mechanically ventilated patients in the intensive care unit (ICU) are typically turned manually by nursing staff to reduce the risk of developing ventilator associated pneumonia and other problems in the lungs. However, turning can induce changes in the heart rate and blood pressure that can at times have a destabilizing effect. We report here on the early stage of a study that has been undertaken to measure the cardiovascular impact of manual turning, and compare it to changes induced when patients lie on automated beds that turn continuously. Heart rate and blood pressure data were analyzed over ensembles of turns with autoregressive models for comparing baseline level to the dynamic response. Manual turning stimulated a response in the heart rate that lasted for a median of 20 minutes and was of magnitude 5 to 13 bpm. The corresponding response in mean arterial pressure was 11 to 19 mm Hg, lasting for 8 to 21 minutes. There was no discernible response of either variable to automated turns.

Adverse hemodynamic effects of lateral rotation during mechanical ventilation.

Turning critically ill, mechanically ventilated patients every 2 hours is a fundamental nursing intervention to reduce the negative impact of prolonged immobility from preventable pulmonary complications such as ventilator-associated pneumonia and atelectasis. Unfortunately, when coupled with positive pressure ventilation, the benefits of turning may come at the expense of cardiovascular function. Clinicians should closely monitor the hemodynamic response to turning mechanically ventilated patients, and if compromise is observed, the degree and duration of compromise may provide guidance to the appropriate intervention.

Microcirculatory Alterations in Shock States

Functional components of the microcirculation provide oxygen and nutrients and remove waste products from the tissue beds of the bodys organs. Shock states overwhelmingly stress functional capacity of the microcirculation, resulting in microcirculatory failure. In septic shock, inflammatory mediators contribute to hemodynamic instability. In nonseptic shock states, the microcirculation is better able to compensate for alterations in vascular resistance, cardiac output, and blood pressure. Therefore, global hemodynamic and oxygen delivery parameters are appropriate for assessing, monitoring, and guiding therapy in hypovolemic and cardiogenic shock but, alone, are inadequate for septic shock.