CHF References ============== al-Furaih, T. A., J. C. McElnay, et al. (1991). "Sublingual captopril--a pharmacokinetic and pharmacodynamic evaluation." Eur J Clin Pharmacol 40(4): 393-8. In this study we compared the pharmacokinetics and pharmacodynamics of captopril after sublingual and peroral administration. Single 25 mg doses of captopril were administered sublingually and perorally on two different occasions in a randomised cross-over fashion to eight healthy volunteers aged 22-35 years. The kinetics of unchanged captopril, plasma renin activity (PRA). BP and heart rate were studied over three hours after both peroral and sublingual administration of captopril. Mean pharmacokinetic parameters for unchanged captopril after sublingual administration were: Cmax, 234 ng.ml-1; tmax, 45 min; AUC (0-3 h), 15.1 micrograms.ml-1.min. Mean pharmacokinetic parameters for unchanged captopril after peroral administration were; Cmax, 228 ng.ml-1; tmax, 75 min; AUC (0-3 h), 17.0 micrograms.ml-1.min.tmax was significantly shorter when captopril was administered sublingually; all other pharmacokinetic parameters were equivalent. The plasma captopril concentrations achieved post drug administration led to increases in PRA and reductions in BP.tmax for PRA was 86 min for sublingual captopril and 113 min for perorally administered drug. Peak PRA values were, however, not significantly different. BP, as expected, was not reduced dramatically in these healthy volunteer subjects, however, in systolic BP vs time profiles, BP was significantly lower after volunteers received sublingual captopril. Heart rate increased slightly after captopril administration; there were no differences between the two routes of administration. Administration of captopril sublingually, therefore led to a more rapid attainment of plasma captopril concentrations and had a more rapid onset of pharmacological effect when compared with peroral administration. Arzi, H., G. Ben-Dror, et al. (2002). "[Angioedema of the tongue and oropharynx after treatment with sublingual captopril]." Harefuah 141(10): 869-70, 931. Angioedema of the tongue and oropharynx is a rare and potentially life threatening adverse reaction related to the use of angiotensin converting enzyme inhibitors. We report a case of a patient who suffered angioedema of the tongue following sub-lingual Captopril treatment and discuss the prevalence, prevention and treatment of this adverse event. This case report is an addition to a limited number of similar cases and denotes the severity of this phenomenon and the need to be aware of its existence. Barbier, P., G. Tamborini, et al. (1996). "Acute filling pattern changes of the failing left ventricle after captopril as related to ventricular structure." Cardiology 87(2): 153-60. In congestive heart failure captopril modifies the left ventricular filling pattern mainly by unloading the heart. We investigated whether the structural characteristics of the left ventricle may influence the acute effects of captopril on this pattern in patients with untreated hypertensive (H group, 6 patients) or idiopathic (I group, 14 patients) cardiomyopathy. We evaluated changes of pulsed Doppler mitral flow, of systemic arterial and wedge pulmonary pressures 40 min after 25 mg captopril administered sublingually, and correlated these changes with the M-mode echocardiographic relative wall thickness index (h/r). Baseline mean arterial pressure (H = 137 +/- 20 mm Hg, mean +/- SD, I = 95 +/- 19 mm Hg; p < 0.001), and h/r (H = 0.38 +/- 0.03, I = 0.28 +/- 0.09; p < 0.05) were greater in the high blood pressure group; wedge pressure, echocardiographic biplane ejection fraction, and Doppler indexes of the left ventricular filling were similar in the two populations. After captopril, ejection fraction did not change significantly, mean arterial pressure decreased significantly in hypertensive patients (H group, baseline = 137 +/- 20, captopril = 119 +/- 10, p = 0.02; I group, baseline = 95 +/- 19, captopril = 90 +/- 24, p = nonsignificant), and the wedge pressure was reduced by the same extent in both groups (H group, baseline = 27.7 +/- 3, captopril = 21 +/- 7, p < 0.05; I group, baseline = 20 +/- 12, captopril = 15 +/- 8, p < 0.05). In the H group early mitral flow increased [(E wave integral) x (mitral annulus area)] by 38 +/- 15%, and was almost steady in the I group (-1.3 +/- 30%; group H vs. I = p < 0.01); late mitral flow [(A wave integral) x (mitral annulus area)] showed a pattern exactly opposite to this (H = +0.4 +/- 40%, I = +38 +/- 19; p < 0.01). In the whole population there was a significant correlation between the early/late flow ratio variations and baseline h/r (r = 0.6, p < 0.05). In chronic congestive heart failure, changes in left ventricular filling with captopril are related to h/r: a higher index, as recorded in the H group, is associated with "true normalization' of the filling pattern after captopril; a lower index, as recorded in the I group, is associated with "pseudonormalization' despite a similar decrease of left ventricular filling pressure. Belz, G. G. and C. De Mey (1992). "A case for sublingual captopril." Blood Press 1(2): 120-2. Capewell, S., D. Taverner, et al. (1989). "Acute and chronic arterial and venous effects of captopril in congestive cardiac failure." Bmj 299(6705): 942-5. OBJECTIVE--To determine whether captopril alters peripheral venous tone in patients with congestive cardiac failure. DESIGN--Open study of patients at start of captopril treatment and three months later. SETTING--A hospital gamma camera laboratory. PATIENTS--16 Men with congestive cardiac failure in New York Heart Association class II or III, aged 57-73. INTERVENTIONS--Patients were initially given 500 micrograms sublingual glyceryl trinitrate followed by 25 mg oral captopril. The study was then repeated after three months' captopril treatment. MAIN OUTCOME MEASURES--Previously validated non-invasive radionuclide techniques were used to measure changes in central haemodynamic variables and peripheral venous volumes in the calf. RESULTS--After 25 mg captopril there were falls in blood pressure and relative systemic vascular resistance and increases in cardiac index and left ventricular ejection fraction. This was accompanied by a 16% increase in peripheral venous volume (95% confidence interval 13.4% to 18.4%, p less than 0.01), which compared with an 11% increase after 500 micrograms glyceryl trinitrate (10% to 12%, p less than 0.01). Eleven patients were restudied after three months' continuous treatment with captopril. The resting venous volume was higher than it had been initially, by about 10%, and increased by a further 8.4% after 25 mg captopril (5.4% to 11.4%, p less than 0.05). CONCLUSIONS--Captopril is an important venodilator. Venous and arterial dilatation are produced short term and during long term treatment. Chetty, D. J., L. L. Chen, et al. (2001). "Characterization of captopril sublingual permeation: determination of preferred routes and mechanisms." J Pharm Sci 90(11): 1868-77. Although sublingual captopril has been used clinically to treat hypertensive emergencies, a mechanistic understanding of sublingual permeation will facilitate the optimization of drug delivery. A correlation of sublingual steady-state flux with donor captopril concentration in a porcine model showed the absence of saturability and suggested a passive diffusion permeation mechanism. A simultaneous evaluation of permeability and partition coefficient demonstrated that the paracellular route is the predominant pathway for sublingual permeation. The enhancement factors of specific ion permeabilities in the presence of tight junction perturbants indicated that although the paracellular pathway is preferred by the ionized species of captopril, the lipophilic transcellular pathway is preferred by the neutral, un-ionized species. Dhawan, S., D. Soni, et al. (1992). "Use of captopril as an isolated agent for the management of stable angina pectoris--a double blind randomised trial." Indian Heart J 44(3): 151-4. In this double blind randomised placebo controlled study, we investigated the antianginal efficacy of oral captopril in 33 patients of angiographically documented coronary artery disease (chronic stable angina). Apart from sublingual nitrates, all other antianginal drugs were withdrawn. Patients were then evaluated both subjectively by questionnaire and objectively by treadmill stress test. No patient had more than mild hypertension and all patients had good left ventricular function. One group of patients received oral captopril while the other group was given placebo. A repeat assessment was done after six weeks and the results compared with baseline. Anginal attacks decreased from 20.11 +/- 1.86 per week on placebo to 9.92 +/- 1.38 (p < 0.01) on captopril as also the number of sublingual nitrates (18.84 +/- 3.01 to 11.14 +/- 2.94, p < 0.01). Assessment by the treadmill stress test showed that in comparison to the pretreatment test, captopril therapy resulted in a significantly increased exercise duration (6.26 +/- 0.21 to 6.98 +/- 0.31 minutes, p < 0.05), total work done (6.76 +/- 0.26 METS to 7.48 +/- 0.29 METS, p < 0.05). In addition there was a significant increase in time to angina (6.16 +/- 0.18 to 6.85 +/- 0.24 min, p < 0.05) and time to 1mm ST depression (5.18 +/- 0.26 to 6.46 +/- 0.30 min, p < 0.01). We conclude that captopril is an effective monotherapy for patients with chronic stable angina and has both antianginal as well as anti-ischemic effects, possibly secondary to direct coronary vasodilation. Gemici, K., I. Baran, et al. (2003). "Evaluation of the effect of the sublingually administered nifedipine and captopril via transcranial doppler ultrasonography during hypertensive crisis." Blood Press 12(1): 46-8. OBJECTIVE: This study was designed to show the effects of sublingually administered nifedipine and captopril on middle cerebral arterial blood flow during hypertensive crisis in the emergency department. METHODS AND RESULTS: Transcranial Doppler ultrasonography (TCD) was performed on the patients fulfilling the criteria (15 patients given captopril, 13 patients given nifedipine, mean (+/-SD) age 56 +/- 11 and 54 +/- 10 years, respectively). Then, patients were randomized into sublingually administered captopril or nifedipine groups and after the drug administration, TCD was repeated. Initial systolic and diastolic blood pressures were 200 +/- 21/125 +/- 21 mmHg in the captopril group and 199 +/- 17/ 123 +/- 20 mmHg in the nifedipine group. There was no significant difference between antihypertensive effects of the drugs after initiation of treatment. Before the treatment with captopril, middle cerebral artery (MCA) flow velocities (Vm) and pulsatility index (PI) were 76.74 +/- 6.38 cm/s and 1.18 +/- 0.09, respectively. The values after the treatment with captopril were 78.21 +/- 5.24cm/s (p < 0.05) and 0.92 +/- 0.08 (p < 0.001), respectively. Before the treatment with nifedipine, Vm and PIs were 64.73 +/- 5.11 cm/s and 1.14 +/- 0.18, respectively. After the treatment with nifedipine, Vm was 60.04 +/- 5.36 cm/s (p < 0.01) and PI was 1.21 +/- 0.09 (p < 0.01). CONCLUSION: After treatment with captopril, PIs were decreased to normal limits but in the group treated with nifedipine, PIs increased to more pathological values. These results showed that we should reconsider the use of nifedipine in the emergency departments as an antihypertensive agent in hypertensive attack treatment. Halon, D. A., T. Rosenfeld, et al. (1988). "Advantage of combined therapy with captopril and nitrates in severe congestive heart failure." Isr J Med Sci 24(11): 664-70. We compared the acute hemodynamic effects of captopril and nitrates in 11 patients with severe congestive heart failure and Grade IV cardiac disability. Pressures were measured using a Swan-Ganz catheter system; cardiac output and stroke index were measured by thermodilution, and left-ventricular (LV) volumes and ejection fraction were calculated simultaneously with the hemodynamic measurements from radionuclide ventriculography. Measurements were made in each of four treatment states: control, sublingual isosorbide dinitrate (ISDN) (5 and 15 mg), oral captopril (50 to 200 mg daily) and during combined therapy with captopril and ISDN. Captopril produced a fall in mean arterial pressure (P less than 0.01) from 81 +/- 14 to 72 +/- 13 mm Hg, and a rise in stroke index from 30 +/- 5 to 35 +/- 91/min per m2 (P less than 0.05), while LV ejection fraction increased from 18 +/- 5 to 21 +/- 7% (P less than 0.05). ISDN reduced mean arterial, pulmonary arterial, right-atrial and wedge pressure. The combination of captopril and ISDN produced a greater fall in mean arterial pressure, a further rise in ejection fraction to 22 +/- 8% (P less than 0.05), a fall in systemic (P less than 0.05) and pulmonary vascular resistance (P less than 0.01) and a rise in cardiac (P less than 0.01) and stroke work index (P less than 0.01), while the beneficial effects of ISDN on right-atrial, pulmonary arterial and wedge pressure were again achieved. LV contractility, assessed from end-systolic stress-shortening relations, was essentially unaltered or decreased very slightly. The study showed that combined therapy with captopril and nitrates produced acute hemodynamic benefits superior to those achieved by treatment with captopril or nitrates alone. Halon, D. A., T. Rosenfeld, et al. (1994). "[The benefit of combined therapy with captopril and nitrates in severe congestive heart failure]." Cardiology 84 Suppl 1: 43-51. We compared the acute hemodynamic effects of captopril and nitrates in 11 patients with severe congestive heart failure and grade IV cardiac disability. Pressures were measured using a Swan-Ganz catheter system; cardiac output and stroke index were measured by thermodilution, and left-ventricular (LV) volumes and ejection fraction were calculated simultaneously with the hemodynamic measurements from radionuclide ventriculography. Measurements were made in each of 4 treatment states: control, sublingual isosorbide dinitrate (ISDN; 5 and 15 mg), oral captopril (50-200 mg daily) and during combined therapy with captopril and ISDN. Captopril produced a fall in mean arterial pressure (p < 0.01) from 81 +/- 14 to 72 +/- 13 mm Hg and a rise in stroke index from 30 +/- 5 to 35 +/- 91/min/m2 (p < 0.05), while LV ejection fraction increased from 18 +/- 5 to 21 +/- 7% (p < 0.05). ISDN reduced mean arterial, pulmonary arterial, right-atrial and wedge pressure. The combination of captopril and ISDN produced a greater fall in mean arterial pressure, a further rise in ejection fraction to 22 +/- 8% (p < 0.05), a fall in systemic (p < 0.05) and pulmonary vascular resistance (p < 0.01) and a rise in cardiac (p < 0.01) and stroke work index (p < 0.01), while the beneficial effects of ISDN on right-atrial, pulmonary arterial and wedge pressure were again achieved. LV contractility, assessed from end-systolic stress-shortening relations, was essentially unaltered or decreased very slightly. The study showed that combined therapy with captopril and nitrates produced acute hemodynamic benefits superior to those achieved by treatment with captopril or nitrates alone. Hamilton, R. J., W. A. Carter, et al. (1996). "Rapid improvement of acute pulmonary edema with sublingual captopril." Acad Emerg Med 3(3): 205-12. OBJECTIVE: To test the hypothesis that sublingual captopril produces a more rapid improvement of acute pulmonary edema (APE) than does placebo, when added to a standard regimen of O2, nitrates, morphine, and furosemide. METHODS: Prospective, randomized, double-blind, placebo-controlled clinical trial in an urban teaching hospital ED. Adults brought to the ED with APE were given captopril or placebo sublingually. Every 5 minutes a clinical APE distress score (APEX) was obtained. RESULTS: Over the first 40 minutes of treatment, the mean APEXs were significantly better for the patients given captopril [p < 0.001, F = 14.5, one-way (repeated-measures) analysis of variance (ANOVA)]. At 30 minutes, the patients given captopril had a mean APEX improvement of 43% (i.e., to 57% of initial distress); the group given the current standard regimen plus placebo improved only 25% (i.e., to 75% of initial distress; p = 0.03, multiway ANOVA). In addition, there was less respiratory failure necessitating mechanical ventilation in the captopril patients (9%) vs the placebo patients (20%), which did not achieve significance (p = 0.10, Fisher's exact test). CONCLUSION: In APE, the addition of sublingual captopril to the standard regimen of O2, nitrates, morphine, and furosemide produces more rapid clinical improvement than does the standard regimen alone. Haude, M., W. Steffen, et al. (1990). "Sublingual administration of captopril versus nitroglycerin in patients with severe congestive heart failure." Int J Cardiol 27(3): 351-9. Angiotensin-converting enzyme inhibition has proven to be a successful approach for the long-term treatment of patients with congestive heart failure. This investigation compared the acute hemodynamic changes after sublingual administration of the angiotensin-converting enzyme inhibitor captopril with those after nitroglycerin. A total of 24 patients with severe left heart failure (New York Heart Association classes III and IV) were given 25 mg captopril and 0.8 mg nitroglycerin sublingually in this randomized, cross-over study. Hemodynamic monitoring revealed a clear improvement in pre- and afterload parameters for both drugs (P less than 0.01 and P less than 0.001), while captopril induced a higher increase in cardiac index (+49.2% vs. +25%), stroke volume index (+53.5% vs. +25.7%), and stroke work index (+55% vs. +28%) than nitroglycerin (P less than 0.001). Although not statistically significant, the onset of change for most hemodynamic parameters was measured earlier after nitroglycerin (after 12-19 vs. 16-22 minutes). Captopril revealed later peak effects (after 47-84 vs. 25-55 minutes, P less than 0.001) and a longer sustained improvement in hemodynamic values (return to baseline values after 117-162 vs. 68-120 minutes, P less than 0.001). No side effects occurred after either captopril or nitroglycerin in this study. Thus, these results indicate there is an early improvement in hemodynamic parameters after the sublingual administration of both drugs in patients with severe congestive heart failure, and that captopril induces a more pronounced and prolonged improvement than nitroglycerin. Haude, M., W. Steffen, et al. (1989). "[Hemodynamics after sublingual administration of captopril in severe heart failure. A pilot study]." Dtsch Med Wochenschr 114(28-29): 1095-100. In a preliminary trial, 23 patients in severe left-heart failure and, in some instances, also right-heart failure (NYHA classes III and IV) received a single sublingual dose of 25 mg captopril. Invasive measurement of various haemodynamic parameters indicated (1) an increase in cardiac index and stroke-volume index of 34% and 38%, respectively (P less than 0.001 for each); (2) decrease in pulmonary artery and systemic pressures by an average of 7% and 11.4% (P less than 0.01 and less than 0.001, respectively); (3) no significant change in heart rate and mean right atrial pressure; (4) decrease in systemic and pulmonary artery resistance by 33% and 29% (P less than 0.001 for both); (5) an increase in left ventricular stroke work index by 18% (P less than 0.001); and (6) a fall in heart rate x pressure product by 10% (P less than 0.005). These haemodynamic changes started within 12 to 23 minutes after captopril administration, the peak effect occurring between 40 and 90 minutes. Baseline values were reached after three hours. Reproducibility measurements revealed a close quantitative and temporal correlation (r for all greater than 0.8). To obtain similar changes of cardiac function 1.65 micrograms/min.kg sodium nitroprusside were needed. The results indicate that sublingual administration of captopril in severe heart failure will achieve early and significant improvement in cardiac function. Katz, R. J., W. S. Levy, et al. (1991). "Prevention of nitrate tolerance with angiotension converting enzyme inhibitors." Circulation 83(4): 1271-7. BACKGROUND. Activation of neurohumoral hormones or sulfhydryl group depletion may contribute to the development of nitroglycerin tolerance. In an attempt to prevent nitrate tolerance, this study evaluated the interaction of nitroglycerin with angiotensin converting enzyme (ACE) inhibitors with and without a sulfhydryl group. METHODS AND RESULTS. Thirty-four subjects were randomized to a 7-day regimen of enalapril 10 mg b.i.d., captopril 25 mg t.i.d., or placebo. Venodilator response to nitroglycerin was assessed with forearm plethysmography by measuring the change in venous volume after administration of 0.4 mg sublingual nitroglycerin. Plethysmographic measurements were obtained serially 1) at baseline, 2) after 4 days of ACE inhibitor or placebo, 3) 2 hours after application of a 10 mg/24 hr nitroglycerin patch, and 4) 74 hours after continuous nitropatch application. ACE inhibition alone caused no significant change in the response to sublingual nitroglycerin. Nitrate response remained unchanged after 2 hours ("acute") of nitropatch exposure in all three groups. After 74 hours ("chronic") of continuous nitropatch application, the venodilator response to sublingual nitroglycerin was reduced by 40% in the placebo group, 10% in the enalapril group, and 2% in the captopril group. This attenuation was significant only in the placebo group (p less than 0.01). Pairwise comparison of nitrate response between groups was significantly different between the captopril and placebo groups (p less than 0.01) and between the placebo and enalapril groups (p less than 0.05). Plasma renin levels increased equally in the enalapril and captopril groups. Body weight increased only in the placebo group, suggesting prevention of nitrate-induced volume expansion in the ACE inhibitor groups. CONCLUSIONS. This study demonstrates that ACE inhibitors may prevent nitrate tolerance to long-term nitrate therapy. Lewis, B. S., D. A. Halon, et al. (1987). "Effect of captopril on left ventricular end-systolic pressure-volume and stress-shortening relations in severe cardiac failure." Clin Cardiol 10(6): 340-4. The effects of captopril on cardiovascular dynamics and left ventricular (LV) contractility were studied in 11 patients with severe congestive heart failure and very poor global LV function. Pressures were measured using a flow-guided catheter, cardiac output by thermodilution, and LV contraction and ejection fraction by simultaneous radionuclide angiography. Ventricular loading conditions were altered by sublingual isosorbide dinitrate to facilitate construction of LV pressure-volume and stress-shortening curves. Captopril decreased mean arterial pressure (p less than 0.02) and systemic vascular resistance, while stroke and cardiac index increased in most patients. Left ventricular ejection fraction increased from 18 +/- 5 to 22 +/- 7% (p less than 0.05), but contractility, assessed from end-systolic pressure-volume and end-systolic pressure-shortening relations, was unchanged or decreased slightly. Heart rate and double product also tended to decrease. In contrast, arteriovenous oxygen difference widened and calculated total oxygen consumption increased during captopril therapy (p less than 0.05). The study showed that captopril improved forward blood flow, total oxygen extraction, and LV ejection fraction following the decrease impedance to LV emptying but not at the expense of an increase in ventricular contractility. This makes captopril an attractive drug for patients with end-stage cardiac failure and a severely damaged myocardium. McElnay, J. C., T. A. al-Furaih, et al. (1996). "A pharmacokinetic and pharmacodynamic evaluation of buffered sublingual captopril in patients with congestive heart failure." Eur J Clin Pharmacol 49(6): 471-6. OBJECTIVE. The pharmacokinetics and pharmacodynamics of buffered sublingual captopril were assessed in patients with congestive heart failure (CHF). METHODS. The study was carried out in a randomised single-blind cross-over fashion (n = 6, 4 males and 2 females) and involved two study days, at least 7 days apart. Baseline measurements were carried out for plasma renin activity (PRA), blood pressure (B.P.) and heart rate (H.R.). Captopril (12.5 mg) was administered sublingually with dibasic potassium phosphate which maintained salivary pH at 7, or perorally with 100 ml of water. Further B.P., H.R. measurements and venous blood samples were taken over a 3 hour period post-drug administration. Blood samples were analysed for captopril and PRA levels. RESULTS. tmax after buffered sublingual administration of captopril, which ranged from 40-60 min (median = 40 min), was significantly shorter than after peroral administration (range 60-120 min, median = 90 min). Cmax was slightly greater after buffered sublingual than after peroral administration with mean values of 108.2 vs. 94.0 ng.ml-1. AUC values were similar after both routes of administration. Systolic and diastolic B.P. vs. time profiles for each administration method were significantly different i.e. sublingual administration produced an earlier reduction in B.P., however, HR did not differ significantly between the two routes. CONCLUSION. The data indicate that this novel administration method of captopril leads to an increased rate, but an unchanged extent of captopril absorption, suggesting a modest therapeutic advantage with the use of buffered sublingual captopril if a rapid reduction in blood pressure is required. Mourao, L., J. M. Santos, et al. (1991). "[Hemodynamic effects of captopril in acute infarct of the anterior myocardium]." Rev Port Cardiol 10(4): 309-12. OBJECTIVE: Evaluation of haemodynamic effects after sublingual administration of 25 mg of captopril in patients with Acute Anterior Myocardial Infarction within the first 48 hours. DESIGN: Determination of basal parameters and 30 minutes after 25 mg of captopril. SETTING: Patients admitted in the ICU with Anterior Myocardial Infarction diagnosis. PATIENTS: 41 consecutive patients; 22 patients submitted to thrombolysis with streptokinase; 19 patients submitted to conventional therapy. RESULTS: A) In the whole group: No significant change in the HR, PAP, CI, SI, MAP, SVR, PR. RA and CWP were reduced. B) In thrombolysed patients: No significant change in HR, RA, PAP, CWP, MAP, SVR, PR. CI and SI were significantly increased. C) In non-thrombolysed patients: No significant change in HR, PAP, CI, SI, SVR, PR. RA, CWP and MAP were reduced. CONCLUSION: 1. We found no significant hypotension with sublingual captopril in Acute Myocardial Infarction. 2. Non-thrombolysed patients showed a greater reduction of arterial pressure. 3. Thrombolysed patients had significant increases in systolic function indices. Sacchetti, A., J. McCabe, et al. (1993). "ED management of acute congestive heart failure in renal dialysis patients." Am J Emerg Med 11(6): 644-7. This is a descriptive report of the management techniques used effectively in the emergency department (ED) treatment of acute congestive heart failure (CHF) in renal dialysis patients. Study design included a prospective case series of consecutive renal dialysis patients who presented to the ED of a regional dialysis center in acute CHF. Clinical presentation, ED management, and outcome were recorded. Forty-six patients (38 hemodialysis and 8 peritoneal dialysis) were included in this study. Presentation classifications for these patients were minimal distress (13 patients), moderate distress (16 patients), and severe distress (17 patients). In addition to supplemental oxygen, treatment focused on pharmacological preload and afterload reduction. Patients received sublingual nitroglycerin (NTG) (30 patients), transdermal NTG (36 patients), captopril sublingual (10 patients) nifedipine oral (nine patients), nitroprusside (four patients), morphine sulfate (one patient), NTG infusion (one patient), and clonidine (one patient). There were no deaths in the study group, and 32 of the patients were able to be dialyzed and discharged, including seven patients in the severe group. Six patients required intubation, one of whom was extubated and discharged from the ED after dialysis. Intravascular access was obtained in 29 patients but was used in only six. All patients on nitroprusside drips were weaned during the course of their dialysis. Effective ED management of acute CHF in renal dialysis patients can be accomplished through preload reduction with nitrates and afterload reduction with captopril, nifedipine, and, in severe cases, nitroprusside. Sacchetti, A., E. Ramoska, et al. (1999). "Effect of ED management on ICU use in acute pulmonary edema." Am J Emerg Med 17(6): 571-4. Acute pulmonary edema (APE) is a common Emergency Department (ED) presentation requiring admission to an intensive care unit (ICU). This study was undertaken to examine the effect of ED management on the need for ICU admission in patients with APE. ED records of APE patients were abstracted for patient age, prehospital and ED pharmacological treatment, diagnoses, airway interventions, and ICU length of stay (LOS). Statistical analysis was through multiple regression, logistic regression, chi-square, and ANOVA. One hundred eighty-one patients composed the study group. Pharmacological treatment included nitroglycerin (NTG), 147 patients (81%); morphine sulfate (MS), 88 (49%); loop diuretics (LD), 133 (73%); and captopril sublingual (CSL), 47 (26%). Use of CSL and MS were associated with opposing needs for ICU admission. MS use was associated with increased ICU admissions (odds ratio, 3.08; P =.002), whereas CSL use was associated with decreased ICU admissions (odds ratio, 0.29; P =.002). Morphine sulfate use also demonstrated an increased need for endotracheal intubation (ETI) (odds ratio, 5.04; P =.001), whereas CSL demonstrated a decreased need for ETI (odds ratio, 0.16; P =.008). Ninety-three patients required some form of respiratory support. Forty received noninvasive pressure support ventilation (NPSV) from a bilevel positive airway pressure system (BiPAP), and 60 received endotracheal intubation. Some patients received more than 1 form of respiratory support; all other patients received supplemental oxygen only. The ICU-LOS associated with different airway interventions were supplemental oxygen, 0.72 days; BiPAP, 1.48 days; and ETI, 3.70 days (P <.001). Specific ED pharmacological interventions are associated with a decreased need for ICU admission and endotracheal intubation in acute pulmonary edema patients, whereas use of noninvasive pressure support ventilation correlates with a reduction in the ICU length of stay for patients who do require critical care admission. Wolk, R., P. Kulakowski, et al. (1996). "Nifedipine and captopril exert divergent effects on heart rate variability in patients with acute episodes of hypertension." J Hum Hypertens 10(5): 327-32. Acute changes of heart rate variability (HRV) depict alterations in autonomic influences on cardiovascular system and often precede ventricular arrhythmias. The aim of the study was to assess effects of sublingual 10 mg nifedipine (n = 15) or 25 mg captopril (n = 13) on HRV in consecutive patients admitted to hospital due to severe hypertension. HRV was calculated on-line from 300 cardiac cycles before and 60-90 min after drug administration. At baseline systolic blood pressure (SBP) was > 190 mm Hg and/or diastolic blood pressure (DBP) > 110 mm Hg. Both agents caused similar reduction of blood pressure (BP). Nifedipine reduced variance (-63 +/- 6%; P < 0.0001) and high-frequency (HF) component (-72 +/- 8%; P < 0.0001), and increased both LF/HF ratio (+870 +/- 336%; P < 0.02) and heart rate (+14 +/- 3%; P < 0.0001). Captopril exerted different effects: variance and HF component increased by +176 +/- 55%; (P < 0.007) and +126 +/- 44% (P < 0.015), respectively. LF/HF (low/high frequency) ratio decreased (-44 +/- 19%; P < 0.04) together with heart rate (-4 +/- 1%; < 0.009). It is concluded that captopril, in contrast to nifedipine, increases HRV and decreases LF/HF ratio and therefore is a better choice in hypertensive patients who might be prone to dangerous arrhythmias. TITLE Rapid improvement of acute pulmonary edema with sublingual captopril [see comments] COMMENTS Comment in: Acad Emerg Med 1996 Mar;3(3):192-3 AUTHOR(S) Hamilton-RJ; Carter-WA; Gallagher-EJ ADDRESS OF AUTHOR New York University, New York, USA. hamilton@is2.nyu.edu SOURCE (BIBLIOGRAPHIC CITATION) Acad-Emerg-Med.1996 Mar; 3(3): 205-12. PUBLICATION YEAR 1996 ABSTRACT OBJECTIVE: To test the hypothesis that sublingual captopril produces a more rapid improvement of acute pulmonary edema (APE) than does placebo, when added to a standard regimen of O2, nitrates, morphine, and furosemide. METHODS: Prospective, randomized, double-blind, placebo-controlled clinical trial in an urban teaching hospital ED. Adults brought to the ED with APE were given captopril or placebo sublingually. Every 5 minutes a clinical APE distress score (APEX) was obtained. RESULTS: Over the first 40 minutes of treatment, the mean APEXs were significantly better for the patients given captopril [p < 0.001, F = 14.5, one-way (repeated-measures) analysis of variance (ANOVA)]. At 30 minutes, the patients given captopril had a mean APEX improvement of 43% (i.e., to 57% of initial distress); the group given the current standard regimen plus placebo improved only 25% (i.e., to 75% of initial distress; p = 0.03, multiway ANOVA). In addition, there was less respiratory failure necessitating mechanical ventilation in the captopril patients (9%) vs the placebo patients (20%), which did not achieve significance (p = 0.10, Fisher's exact test). CONCLUSION: In APE, the addition of sublingual captopril to the standard regimen of O2, nitrates, morphine, and furosemide produces more rapid clinical improvement than does the standard regimen alone. (1) Hamilton RJ. Rapid improvement of acute pulmonary edema with sublingual captopril. Acad Emerg Med 1996;3:205-212 . OBJECTIVE: To test the hypothesis that sublingual captopril produces a more rapid improvement of acute pulmonary edema (APE) than does placebo, when added to a standard regimen of O2, nitrates, morphine, and furosemide. METHODS: Prospective, randomized, double-blind, placebo-controlled clinical trial in an urban teaching hospital ED. Adults brought to the ED with APE were given captopril or placebo sublingually. Every 5 minutes a clinical APE distress score (APEX) was obtained. RESULTS: Over the first 40 minutes of treatment, the mean APEXs were significantly better for the patients given captopril [p < 0.001, F = 14.5, one-way (repeated-measures) analysis of variance (ANOVA)]. At 30 minutes, the patients given captopril had a mean APEX improvement of 43% (i.e., to 57% of initial distress); the group given the current standard regimen plus placebo improved only 25% (i.e., to 75% of initial distress; p = 0.03, multiway ANOVA). In addition, there was less respiratory failure necessitating mechanical ventilation in the captopril patients (9%) vs the placebo patients (20%), which did not achieve significance (p = 0.10, Fisher's exact test). CONCLUSION: In APE, the addition of sublingual captopril to the standard regimen of O2, nitrates, morphine, and furosemide produces more rapid clinical improvement than does the standard regimen alone.