Use of the activated partial thromboplastin time for heparin monitoring.

The objectives of the present study were to evaluate the relationship between heparin concentration and activated partial thromboplastin time (aPTT) results, define a heparin concentration-derived therapeutic range for each aPTT instrument, compare aPTT- and heparin concentration-guided dosage adjustment decisions, and compare laboratory- and bedside aPTT-guided decisions. In phase 1, 102 blood samples were analyzed for bedside and laboratory aPTTs and heparin concentration (used to establish aPTT therapeutic range). In phase 2, 100 samples were analyzed in the same manner. Correlations for aPTT compared with heparin ranged from 0.36 to 0.82. Dosage adjustment decisions guided by the aPTT agreed with those based on heparin concentration 63% to 80% of the time. Laboratory and bedside aPTT dosage adjustment decisions agreed 59% to 68% of the time. The correlation of aPTT with heparin concentration and agreement between aPTT- and heparin-guided decisions vary with the aPTT instrument. Decisions guided by laboratory aPTT results often disagree with decisions guided by bedside aPTT results.

Correlation of activated clotting time and activated partial thromboplastin time to plasma heparin concentration.

STUDY OBJECTIVE: To determine the correlation between activated clotting time (ACT) or activated partial thromboplastin time (aPTT) and plasma heparin concentration. DESIGN: Two-phase prospective study. SETTING: University-affiliated community hospital. PATIENTS: Thirty patients receiving continuous-infusion intravenous heparin. INTERVENTIONS: Measurement of ACT, aPTT and plasma heparin concentrations. MEASUREMENTS AND MAIN RESULTS: Linear and log linear correlations were determined between clotting time tests and heparin concentrations. Linear correlations yielded r values of 0.58 for ACT (p=0.008) and 0.89 for aPTT (p=0.0001). Log linear correlations yielded r values of 0.60 for ACT (p=0.005) and 0.88 for aPTT (p=0.0001). A decision analysis was performed to determine possible consequences of dosage adjustments based on either test in relationship to the decision based on plasma heparin concentration. The decision analysis based on ACT disagreed with corresponding decisions based on plasma heparin concentration in 15 of 30 patients; 13 disagreements may have increased the risk of bleeding, and the other 2 may have increased the risk of thrombosis. Decisions based on aPTT disagreed with corresponding decisions based on plasma heparin concentration in 13 of 30 patients; 2 disagreements may have increased the risk of bleeding, and the other 11 may have increased the risk of thrombosis. CONCLUSION: There are significant statistical linear and log linear correlations between both clotting time tests and plasma heparin concentrations, with aPTT showing stronger correlation than ACT. However, decisions regarding heparin therapy based on ACT may increase a patient's risk of bleeding, whereas decisions based on aPTT may increase the risk of thrombus progression or rethrombosis.

Pharmaceutical care in medical progressive care patients.

OBJECTIVE: To develop, implement, and assess the outcomes of a system for providing pharmaceutical care to medical progressive care patients. METHODS: A system for providing pharmaceutical care was developed and implemented for an 8-week period beginning in June 1995. Both patient care outcomes and drug therapy cost change from the intervention period were compared with those of an 8-week baseline period. Variables compared included unit length of stay, hospital length of stay, transfers to the intensive care unit, readmissions, and adverse drug reactions requiring treatment. Differences between periods for these variables were assessed by using chi 2 tests and t-tests with alpha set at p less than 0.05. The clinical significance of the interventions were assessed independently by four physicians: two intensivists and two internists. The total drug therapy cost change from the intervention period was calculated as follows: total cost avoidance from individual recommendations subtracted from the total cost incurred from individual recommendations. RESULTS: The pharmacist evaluated 152 patients during the intervention period. A total of 235 pharmacotherapy recommendations were made on 103 patients, of whom 86.4% were accepted. Significantly fewer adverse drug reactions (ADRs) received treatment during the intervention period (p = 0.027). The mean unit length of stay was lower during the intervention period (4.8 +/- 3.7 d) than during the baseline period (6.0 +/- 5.6 d); however, this difference was not significant (p = 0.053). Individual physician assessment of the pharmacists' recommendations revealed that 75.8% were considered somewhat significant, significant, or very significant. The total drug therapy cost change from the intervention period was -$6534.53. The projected annual drug therapy cost reduction from this study is $42,474.45. CONCLUSIONS: The provision of pharmaceutical care to medical progressive care patients was associated with a substantial decrease in drug therapy cost and a decrease in the number of ADRs that required treatment.

Hyperinflation and expiratory muscle recruitment during NREM sleep in humans.

The purpose of this study was to determine the effect of hyperinflation on expiratory muscle recruitment during NREM sleep in healthy humans. Hyperinflation was produced by negative pressure in a tank ventilator or application of positive end-expiratory pressure (PEEP). Expiratory and inspiratory electromyograms (EMGexp and EMGinsp) were measured using transcutaneously implanted wire and surface electrodes, respectively. During wakefulness, sustained hyperinflation (3-5 min, +0.72 +/- 0.31 L) in the tank respirator caused augmentation of EMGexp (+77%, P less than 0.05) and EMGinsp (+27%, P less than 0.05) in all subjects. Brief hyperinflation with PEEP (5 breaths, +0.53 +/- 0.32 L) augmented EMGexp in 3 of 6 subjects and EMGinsp in 5 of 5 subjects (+98%, P less than 0.05). During NREM sleep, sustained hyperinflation (+0.54 +/- 0.17 L) in the tank respirator caused no change in EMGexp and a small increase in EMGinsp (+9%, P less than 0.001). Brief hyperinflation with PEEP (0.29 +/- 0.10 L) caused no change in EMGexp or EMGinsp. Sustained hyperinflation with PEEP activated EMGexp only in subjects whose end-tidal CO2 increased. We concluded that moderate hyperinflation does not recruit expiratory muscles during NREM sleep as it does during wakefulness.

Ventilatory response to single, high dose estazolam in healthy humans.

The purpose of this study was to determine the effect of oral estazolam at two and three times the usually recommended dosage (2 mg) on ventilation and respiratory drive during wakefulness. Sixty healthy subjects were randomized to receive a single oral dose of either: 1) estazolam 4 mg; 2) estazolam 6 mg; 3) placebo; or 4) morphine 0.15 mg/kg. Predrug and postdrug measurements were obtained for ventilation, respiratory cycle timing, metabolic rate, temperature, and ventilatory and mouth occlusion pressure (P0.1) responses to exogenous CO2. No difference between placebo and the study drugs was noted during eupneic breathing. During administration of exogenous CO2, morphine caused a decrease in the slope of the ventilatory (-0.4 +/- 0.1 L/min/mm Hg, P = .008) and P0.1 (-0.22 +/- 0.06 cm H2O/mm Hg, P = .015) responses. Estazolam (4 and 6 mg) had no effect on the ventilatory response to exogenous CO2. However, estazolam (6 mg) caused the P0.1 at a PCO2 of 57 mm Hg to decrease (-0.67 +/- 0.30 cm H2O, P = .005). The preservation of ventilation with the highest dose of estazolam, despite the decrease in P0.1, indicates that a compensatory strategy independent of respiratory center drive may have been activated. Sedation was a common side effect of estazolam reported in 13% and 53% of subjects at the 4 mg and 6 mg doses, respectively. We conclude that a single, high dose of estazolam does not cause ventilatory depression during wakefulness in healthy subjects.

Effect of lung inflation on pulmonary resistance during NREM sleep.

Previous investigations have demonstrated an inverse relationship between lung volume and airway resistance in awake humans. We wished to examine this relationship in the absence of conscious influences. We therefore studied eight healthy subjects who slept in a tank respirator. Hyperinflation was induced by continuous negative tank pressure while the subjects breathed spontaneously. Ventilation, pulmonary resistance (total pulmonary resistance, seven subjects; upper airway resistance, one subject), diaphragm and genioglossus electromyograms (EMGs), and sleep state were measured. During control NREM sleep, group mean maximal pulmonary resistance was 42.5 cm H2O/L/s (range, 17.4 to 106.4 cm H2O/L/s). During steady-state hyperinflation (mean increase in lung volume = 0.53 L), pulmonary resistance decreased 40% (range, -3 to -90%). Ventilation, sleep state, and end-tidal CO2 were unchanged. Inspiratory muscle EMG was increased in two of two subjects during hyperinflation. Genioglossus EMG was characterized by phasic and tonic activity during the control period in two of two subjects. Both components were decreased during steady-state hyperinflation. When lung volume was returned to baseline, pulmonary resistance and genioglossus EMG increased to baseline levels. We conclude that alteration in lung volume within the tidal volume range significantly alters pulmonary resistance during NREM sleep. This influence occurs independent of chemical stimuli or genioglossal muscle activity, and may be related to traction on neck structures caused by descent of mediastinal structures.

Effect of mechanical loading on expiratory and inspiratory muscle activity during NREM sleep.

We investigated the effect of acute and sustained inspiratory resistive loading (IRL) on the activity of expiratory abdominal muscles (EMGab) and the diaphragm (EMGdi) and on ventilation during wakefulness and non-rapid-eye-movement (NREM) sleep in healthy subjects. EMGdi and EMGab were measured with esophageal and transcutaneous electrodes, respectively. During wakefulness, EMGdi increased in response to acute loading (18 cmH2O.l-1.s) (+23%); this was accompanied by preservation of tidal volume (VT) and minute ventilation (VE). During NREM sleep, no augmentation was noted in EMGdi or EMGab. Inspiratory time (TI) was prolonged (+5%), but this was not sufficient to prevent a decrease in both VT and VE (-21 and -20%, respectively). During sustained loading (12 cmH2O.l-1 s) in NREM sleep, control breaths (C) were compared with the steady-state loaded breaths (SS) defined by breaths 41-50. Steady-state IRL was associated with augmentation of EMGdi (12%) and EMGab (50%). VT returned to control levels, expiratory time shortened, and breathing frequency increased. The net result was the increase in VE above control levels (+5%, P less than 0.01). No change was noted in end-tidal CO2 or O2. We concluded that 1) wakefulness is a prerequisite for immediate load compensation (in its absence, TI prolongation is the only compensatory response) and 2) during sustained IRL, the augmentation of EMGdi and EMGab can lead to complete ventilatory recovery without measurable changes in chemical stimuli.

Ventilatory effects of single, high-dose triazolam in awake human subjects.

The respiratory-depressant effect of the benzodiazepine-derived hypnotic triazolam was investigated with a single oral dose at two and three times the usual dosage in 62 awake normal subjects. A randomized, double-blind protocol compared the following groups: (1) placebo, (2) triazolam, 1.0 mg, (3) triazolam, 1.5 mg, and (4) morphine, 0.15 mg/kg. Differences between predrug and postdrug administration were compared. Minute ventilation (Ve), end-tidal PCO2, and the ventilatory response to CO2 (Ve/PCO2) were preserved with both 1.0 mg and 1.5 mg triazolam compared with placebo. Triazolam caused an increase in breathing frequency (+21% to 50%; p less than 0.05) as a result of a shortening of inspiratory time. Triazolam was associated with a higher Ve corrected for CO2 production and Ve/PCO2 compared with morphine. We concluded that a single dose of triazolam at two and three times the usual level does not cause respiratory depression in awake, normal subjects but does alter respiratory cycle timing causing an increase in breathing frequency.

Effect of airway impedance on CO2 retention and respiratory muscle activity during NREM sleep.

We hypothesized that a sleep-induced increase in mechanical impedance contributes to CO2 retention and respiratory muscle recruitment during non-rapid-eye-movement (NREM) sleep. The effect NREM sleep on respiratory muscle activity and CO2 retention was measured in healthy subjects who increased maximum total pulmonary resistance (RLmax, 1-81 cmH2O.l-1.s) from awake to NREM sleep. We determined the effects of this sleep-induced increase in airway impedance by steady-state inhalation of a reduced-density gas mixture (79% He-21% O2, He-O2). Both arterialized blood PCO2 (PaCO2) and end-tidal PCO2 (PETCO2) were measured. Inspiratory (EMGinsp) and expiratory (EMGexp) respiratory muscle electromyogram activity was measured. NREM sleep caused 1) RLmax to increase (7 +/- 3 vs. 39 +/- 28 cmH2O.l-1.s), 2) PaCO2 and/or PETCO2 to increase in all subjects (40 +/- 2 vs. 44 +/- 3 Torr), and 3) EMGinsp to increase in 8 of 9 subjects and EMGexp to increase in 9 of 17 subjects. Compared with steady-state air breathing during NREM sleep, steady-state He-O2 breathing 1) reduced RLmax by 38%, 2) decreased PaCO2 and PETCO2 by 2 Torr, and 3) decreased both EMGinsp (-20%) and EMGexp (-54%). We concluded that the sleep-induced increase in upper airway resistance accompanied by the absence of immediate load compensation is an important determinant of CO2 retention, which, in turn, may cause augmentation of inspiratory and expiratory muscle activity above waking levels during NREM sleep.

Ventilatory compensation for changes in functional residual capacity during sleep.

The role of conscious factors in the ventilatory compensation for shortened inspiratory muscle length and the potency of this compensatory response were studied in five normal subjects during non-rapid-eye-movement sleep. To shorten inspiratory muscles, functional residual capacity (FRC) was increased and maintained for 2-3 min at a constant level (range of increase 160-1,880 ml) by creating negative pressure within a tank respirator in which the subjects slept. Minute ventilation was maintained in all subjects over the entire range of increased FRC (mean change +/- SE = -3 +/- 1%) through preservation of tidal volume (-2 +/- 2%) despite slightly decreased breathing frequency (-6 +/- 2%). The decrease in frequency (-13 +/- 2%) was due to a prolongation in expiratory time. Inspiratory time shortened (-10 +/- 1%). Mean inspiratory flow increased 15 +/- 3% coincident with an increase in the slope of the moving time average of the integrated surface diaphragmatic electromyogram (67 +/- 21%). End-tidal CO2 did not rise. In two subjects, control tidal volume was increased 35-50% with CO2 breathing. This augmented tidal volume was still preserved when FRC was increased. We concluded that the compensatory response to inspiratory muscle shortening did not require factors associated with the conscious state. In addition, the potency of this response was demonstrated by preservation of tidal volume despite extreme shortening of the inspiratory muscles and increase in control tidal volumes caused by CO2 breathing. Finally, the timing changes we observed may be due to reflexes following shortening of inspiratory muscle length, increase in abdominal muscle length, or cardiovascular changes.