Alex Blatt

Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema

BACKGROUND Nitrates and furosemide, commonly administered in the treatment of pulmonary oedema, have not been compared in a prospective clinical trial. We compared the efficacy and safety of these drugs in a randomised trial of patients with severe pulmonary oedema and oxygen saturation below 90%. METHODS Patients presenting to mobile emergency units with signs of congestive heart failure were treated with oxygen 10 L/min, intravenous furosemide 40 mg, and morphine 3 mg bolus. 110 patients were randomly assigned either to group A, who received isosorbide dinitrate (3 mg bolus administered intravenously every 5 min; n=56) or to group B, who received furosemide (80 mg bolus administered intravenously every 15 min, as well as isosorbide dinitrate 1 mg/h, increased every 10 min by 1 mg/h; n=54). Six patients were withdrawn on the basis of chest radiography results. Treatment was continued until oxygen saturation was above 96% or mean arterial blood pressure had decreased by 30% or to below 90 mm Hg. The main endpoints were death, need for mechanical ventilation, and myocardial infarction. The analyses were by intention to treat. FINDINGS Mechanical ventilation was required in seven (13%) of 52 group-A patients and 21 (40%) of 52 group-B patients (p=0.0041). Myocardial infarction occurred in nine (17%) and 19 (37%) patients, respectively (p=0.047). One patient in group A and three in group B died (p=0.61). One or more of these endpoints occurred in 13 (25%) and 24 (46%) patients, respectively (p=0.041). INTERPRETATION High-dose isosorbide dinitrate, given as repeated intravenous boluses after low-dose intravenous furosemide, is safe and effective in controlling severe pulmonary oedema. This treatment regimen is more effective than high-dose furosemide with low-dose isosorbide nitrate in terms of need for mechanical ventilation and frequency of myocardial infarction.

High-dose intravenous isosorbide-dinitrate is safer and better than Bi-PAP ventilation combined with conventional treatment for severe pulmonary edema

OBJECTIVE To determine the feasibility, safety and efficacy of bilevel positive airway ventilation (BiPAP) in the treatment of severe pulmonary edema compared to high dose nitrate therapy. BACKGROUND Although noninvasive ventilation is increasingly used in the treatment of pulmonary edema, its efficacy has not been compared prospectively with newer treatment modalities. METHODS We enrolled 40 consecutive patients with severe pulmonary edema (oxygen saturation <90% on room air prior to treatment). All patients received oxygen at a rate of 10 liter/min, intravenous (IV) furosemide 80 mg and IV morphine 3 mg. Thereafter patients were randomly allocated to receive 1) repeated boluses of IV isosorbide-dinitrate (ISDN) 4 mg every 4 min (n = 20), and 2) BiPAP ventilation and standard dose nitrate therapy (n = 20). Treatment was administered until oxygen saturation increased above 96% or systolic blood pressure decreased to below 110 mm Hg or by more than 30%. Patients whose conditions deteriorated despite therapy were intubated and mechanically ventilated. All treatment was delivered by mobile intensive care units prior to hospital arrival. RESULTS Patients treated by BiPAP had significantly more adverse events. Two BiPAP treated patients died versus zero in the high dose ISDN group. Sixteen BiPAP treated patients (80%) required intubation and mechanical ventilation compared to four (20%) in the high dose ISDN group (p = 0.0004). Myocardial infarction (MI) occurred in 11 (55%) and 2 (10%) patients, respectively (p = 0.006). The combined primary end point (death, mechanical ventilation or MI) was observed in 17 (85%) versus 5 (25%) patients, respectively (p = 0.0003). After 1 h of treatment, oxygen saturation increased to 96 +/- 4% in the high dose ISDN group as compared to 89 +/- 7% in the BiPAP group (p = 0.017). Due to the significant deterioration observed in patients enrolled in the BiPAP arm, the study was prematurely terminated by the safety committee. CONCLUSIONS High dose ISDN is safer and better than BiPAP ventilation combined with conventional therapy in patients with severe pulmonary edema.

Acute heart failure: a novel approach to its pathogenesis and treatment.

Acute heart failure (HF) is one of the most common syndromes in emergency medicine, however, its exact pathogenesis has remained largely unknown. Based on clinical and hemodynamic data we have sub‐divided acute HF into four syndromes: cardiogenic shock, pulmonary edema, hypertensive crisis and exacerbated HF. Cardiogenic shock is caused by a severe reduction in cardiac power which is not met by an adequate increase in peripheral vascular resistance leading to significant decrease in blood pressure and end organ perfusion. Hence the treatment of cardiogenic shock should be directed at improving cardiac performance (by optimizing filling pressure, intra‐aortic balloon pump and immediate revascularization) and administration of peripheral vasoconstrictors. The other acute HF syndromes (pulmonary edema, HTN crisis and exacerbated HF) are caused by a combination of progressive excessive vasoconstriction superimposed on reduced left ventricular functional reserve. The impaired cardiac power and extreme vasoconstriction induce a vicious cycle of afterload mismatch resulting in a dramatic reduction of CO and elevated left ventricular end diastolic pressure, which is transferred backwards to the pulmonary capillaries yielding pulmonary edema. Therefore, the immediate treatment of these acute HF syndromes should be based on the administration of strong, fast‐acting intravenous vasodilators such as nitrates or nitroprusside. After initial stabilization, therapy should be directed at reducing recurrent episodes of acute HF, by prevention of repeated episodes of excessive vasoconstriction along with efforts to optimize cardiac function.

LINCS: L-NAME (a NO synthase inhibitor) in the treatment of refractory cardiogenic shock a prospective randomized study

AIMS To evaluate the effect of L-NAME (a nitric oxide synthase inhibitor) in the treatment of refractory cardiogenic shock. METHODS AND RESULTS We enrolled 30 consecutive patients with refractory cardiogenic shock (systolic blood pressure that deteriorated progressively to <100 mmHg during an acute coronary syndrome despite maximal percutaneous coronary revascularization, intra aortic balloon pump, and IV dopamine, furosemide and fluids treatment for at least 1h, accompanied by signs of peripheral hypoperfusion). Patients were randomized to supportive care alone (n=15, control group) or to supportive care in addition to L-NAME (1mg/Kg bolus and 1mg/Kg/h continuous IV drip for 5h n=15). Death at one month was 27% in the L-NAME group vs. 67% in the control group (p=0.008). Unaugmented mean arterial blood pressure at 24 h from randomization was 86+/-20 mmHg in the L-NAME group vs. 66+/-13 mmHg in the control group (p=0.004). Urine output increased at 24h by 135+/-78 cc/h in the L-NAME group vs a decrease of 12+/-87 cc/h in the control group (p<0.001). Time on IABP and time on mechanical ventilation were significantly shorter in the L-NAME group. CONCLUSIONS The results of the present study further support our previous observation that NO synthase inhibitors are beneficial in the treatment of patients with refractory cardiogenic shock.

A prospective study of posttraumatic stress symptoms and nonadherence in survivors of a myocardial infarction (MI)

We examined a novel hypothesis that links symptoms of MI-related posttraumatic stress disorder (PTSD) to nonadherence. According to this hypothesis, patients who are traumatized by their medical illness do not take their medications as prescribed. As a part of the avoidance dimension of PTSD, patients who are traumatized may avoid being reminded of the MI by not taking the medication. MI survivors were prospectively followed for 6 months to 1 year. Adherence was assessed by pill count of Captopril. Demographic variables, medical risk factors, PTSD, and other psychiatric symptom dimensions were evaluated during follow-up. One hundred two of 140 recruited patients completed follow-up. Nonadherence to Captopril was associated with poor medical outcome (r=.93, P=.006). Above-Threshold PTSD symptoms were associated with nonadherence to medications (P=.05). No other psychiatric symptom dimensions were independently associated with nonadherence. Nonadherence to medications predicts adverse outcome during the first year after an acute MI. Nonadherence is associated with PTSD symptoms, which may either be a marker for or a cause of nonadherence. Treatment of PTSD may prove to be a useful approach for improving adherence.

L-NMMA (a nitric oxide synthase inhibitor) is effective in the treatment of cardiogenic shock.

BACKGROUND The objective was to assess the safety and efficacy of L-NMMA in the treatment of cardiogenic shock. METHODS We enrolled 11 consecutive patients with cardiogenic shock that persisted after >24 hours from admission, despite coronary catheterization and primary percutaneous transluminal coronary revascularization, when feasible, and treatment with mechanical ventilation, intraaortic balloon pump (IABP), and high doses of catecholamines. L-NMMA was administered as an IV bolus of 1 mg/kg and continuous drip of 1 mg. kg(-1). h(-1) for 5 hours. Treatment with catecholamines, mechanical ventilation, and IABP was kept constant throughout the study. RESULTS Within 10 minutes of L-NMMA administration, mean arterial blood pressure (MAP) increased from 76+/-9 to 109+/-22 mm Hg (+43%). Urine output increased within 5 hours from 63+/-25 to 156+/-63 cc/h (+148%). Cardiac index decreased during the steep increase in MAP from 2. 0+/-0.5 to 1.7+/-0.4 L/(min. m(2)) (-15%); however, it gradually increased to 1.85+/-0.4 L/(min. m(2)) after 5 hours. The heart rate and the wedge pressure remained stable. Twenty-four hours after L-NMMA discontinuation, MAP (+36%) and urine output (+189%) remained increased; however, cardiac index returned to pretreatment level. No adverse events were detected. Ten out of eleven patients could be weaned off mechanical ventilation and IABP. Eight patients were discharged from the coronary intensive care unit, and seven (64%) were alive at 1-month follow-up. CONCLUSIONS L-NMMA administration in patients with cardiogenic shock is safe and has favorable clinical and hemodynamic effects.

Minimal heparinization in coronary angioplasty—how much heparin is really warranted?

The purpose of the study was to assess the results of percutaneous transluminal coronary angioplasty (PTCA), performed with a single intravenous bolus of 2,500 U of heparin, in a nonemergency PTCA cohort. Three hundred of 341 consecutive patients (87.9%) undergoing PTCA were prospectively enrolled in the study. They received heparin, 2,500-U intravenous bolus, before PTCA, with intention of no additional heparin administration. Patient and lesion characteristics as well as PTCA results were evaluated independently by 2 physicians. Patients were followed up by structured telephone questionnaires at 1 and 6 months after PTCA. Mean activated clotting time obtained 5 minutes after heparin administration was 185+/-19 seconds (range 157 to 238). There were 3 (1%) in-hospital major adverse cardiovascular events: 2 deaths (0.66%), 1 (0.33%) Q-wave myocardial infarction. Emergency coronary surgery and stroke were not reported. Six patients (2%) experienced abrupt coronary occlusion within 14 days after PTCA, warranting repeat target vessel revascularization. Angiographic and clinical success were achieved in 96% and 93.3%, respectively. No bleeding or vascular complications were recorded. Six-month follow-up (184 patients) revealed 3 cardiac deaths (1 arrhythmic, 2 after cardiac surgery), 1 Q-wave myocardial infarction, and 9.7% repeat target vessel revascularization. This study suggests that very low doses of heparin and reduced activated clotting time target values are safe in non-emergency PTCA, and can reduce bleeding complications, hospital stay, and costs. Larger, randomized, double-blind heparin dose optimization studies need to confirm this notion.

Echocardiographic ejection fraction in patients with acute heart failure : correlations with hemodynamic, clinical, and neurohormonal measures and short-term outcome

Although echocardiographic ejection fraction (EF) is frequently used for the estimation of left ventricular contractility in patients with acute heart failure, its exact role and correlations with clinical, hemodynamic, and neurohormonal variables of cardiac contractility is not known.

Usefulness of losartan, captopril, and furosemide in preventing nitrate tolerance and improving control of unstable angina pectoris

Sixty consecutive normotensive patients with unstable angina pectoris, who were on continuous intravenous isosorbide dinitrate (ISDN) treatment and had not previously received angiotensin II receptor antagonists, angiotensin-converting enzyme (ACE) inhibitors, or diuretics were randomly assigned to treatment groups receiving intravenous ISDN for 72 hours. No additional treatment was given to group A (n = 15). Captopril, in a test dose of 6.25 mg, and followed by 12.5 mg 3 times daily for 24 hours and 25 mg 3 times daily for the next 24 hours, was given to group B (n = 15). The same dose of captopril plus 40 mg of furosemide in the morning were given to group C (n = 15). Losartan, in a single dose of 25 mg/day and increased to 50 mg after 24 hours was given to group D (n = 15). Nitrate tolerance was evaluated at 24-hour intervals at trough levels of each of the drugs by administering intravenous ISDN (1 mg bolus dose every 4 minutes) and recording the total ISDN test dose required to decrease the mean arterial blood pressure by > or =10%. Treatment with continuous ISDN only (group A) induced nitrate tolerance. The ISDN (mean +/- SD) test dose was 3.5 +/- 1.8 mg at baseline, increasing to 4.9 +/- 2.4 mg at 24 hours, and 8.0 +/- 3.0 mg at 48 hours. The addition of increasing doses of captopril to the continuous ISDN treatment (group B) completely prevented nitrate tolerance. Losartan, however, did not attenuate nitrate tolerance at 24 hours and attenuated it only partially at 48 hours. The addition of furosemide to captopril had no further effect on nitrate tolerance. Of 15 patients in group A (ISDN only), 4 (27%) experienced recurrent ischemic events requiring urgent coronary catheterization. No such events were recorded in group B (captopril), but did occur in 1 patient in each of group C (captopril plus furosemide) and D (losartan) (p = 0.083). Thus, the addition of captopril to the ISDN treatment regimen prevented tolerance to nitrates and improved angina control with apparent safety. Losartan also decreased nitrate tolerance, although to a lesser extent, and also improved angina control. The addition of furosemide to captopril conferred no further benefit.

Dermonecrotic Loxoscelism in the Mediterranean Region

AbstractPublications on loxosceles spider bites in the Mediterranean region are scarce. This spider is frequently found in Israel and its bite may cause severe medical problem. We report on 11 patients who sustained such bites and required hospitalization between 1988 and 1997 in a regional hospital serving a population of 300,000. Most of them were bitten in the summer, 10 on the medial aspect of the arm or thigh. All patients exhibited the typical loxosceles skin lesion; systemic manifestations were evident in six. Seven patients were misdiagnosed. All were treated with antibiotics and eight with the addition of corticosteroids. Ten patients fully recovered within 2-3 weeks.The estimated incidence of severe dermonecrotic loxoscelism requiring hospitalization is 0.37 cases/100,000 population/year. It seems that the clinical course in our cases was somewhat milder than in other reported cases from the United States. This can possibly be attributed to the bite of Loxosceles rufescens, which is the prevaili...