Neuromuscular blockade in children

Neuromuscular blocking agents (NMBAs) have been widely used to control patients who need to be immobilized for some kind of medical intervention, such as an invasive procedure or synchronism with mechanical ventilation. The purpose of this monograph is to review the pharmacology of the NMBAs, to compare the main differences between the neuromuscular junction in neonates, infants, toddlers and adults, and moreover to discuss their indications in critically ill pediatric patients. Continuous improvement of knowledge about NMBAs pharmacology, adverse effects, and the many other remaining unanswered questions about neuromuscular junction and neuromuscular blockade in children is essential for the correct use of these drugs. Therefore, the indication of these agents in pediatrics is determined with extreme judiciousness. Computorized (Medline 1990-2000) and active search of articles were the mechanisms used in this review.

Omeprazole, Furazolidone, and Tetracycline: an eradication treatment for resistant H. pylori in Brazilian patients with peptic ulcer disease

OBJECTIVES: To determine the efficacy of a simple, short-term and low-cost eradication treatment for Helicobacter pylori (H. pylori) using omeprazole, tetracycline, and furazolidone in a Brazilian peptic ulcer population, divided into 2 subgroups: untreated and previously treated for the infection. PATIENTS AND METHODS: Patients with peptic ulcer disease diagnosed by endoscopic examination and infected by H. pylori diagnosed by the rapid urease test (RUT) and histological examination, untreated and previously unsuccessfully treated by macrolides and nitroimidazole, were medicated with omeprazole 20 mg daily dose and tetracycline 500 mg and furazolidone 200 mg given 3 times a day for 7 days. Another endoscopy or a breath test was performed 12 weeks after the end of treatment. Patients were considered cured of the infection if a RUT and histologic examination proved negative or a breath test was negative for the bacterium. RESULTS: Sixty-four patients were included in the study. The women were the predominant sex (58%); the mean age was 46 years. Thirty-three percent of the patients were tobacco users, and duodenal ulcer was identified in 80% of patients. For the 59 patients that underwent follow-up examinations, eradication was verified in 44 (75%). The eradication rate for the intention-to-treat group was 69%. The incidence of severe adverse effects was 15%. CONCLUSION: The treatment provides good efficacy for H. pylori eradication in patients who were previously treated without success, but it causes severe adverse effects that prevented adequate use of the medications in 15% of the patients.

Hormone replacement therapy and the risk of breast cancer: assessment of therapy acceptance in a cohort of previously treated breast cancer patients

INTRODUCTION: In the postmenopausal period, an average of 25% of women will present symptomatic ovarian failure requiring hormonal replacement therapy. Estrogen can relieve vasomotor symptoms. Hormonal replacement therapy is generally not recommended for breast cancer patients due to the potential risk of tumor recurrence. To answer the questions about the safety of hormonal replacement therapy in this subgroup of women, it is necessary to establish the acceptance of treatment. METHODS: Between September 1998 and February 2001, a cohort of 216 breast cancer patients were asked to complete a questionnaire. All patients had completed their treatment and were informed about survival rates after breast cancer and hormonal replacement therapy. RESULTS: Among the 216 patients, 134 (62%) would refuse hormonal replacement therapy. A hundred patients were afraid of relapse (74.6%). Adjuvant tamoxifen therapy was the only statistically significant variable (70.3% versus 29.7% p=0.003). Understanding clinical stage (p= 0.045) and type of medical assistance (private versus public , p=0.033) also seemed to influence the decision. Early stage disease (p= 0.22), type of surgical procedure (radical versus conservative, p=0.67), adjuvant chemotherapy (p=0.082) or marital status (p=0.98 ) were not statistically significant in decision making. Several patients submitted to adjuvant chemotherapy (41.6%) would accept hormonal replacement therapy under medical supervision, as did most of advanced clinical stage patients (58.3%; p=0.022). CONCLUSION: There is a high level of rejection for hormonal replacement therapy among breast cancer patients when current data on tumor cure rates, and potential risks of estrogen use is available. Adverse effects of tamoxifen in the adjuvant setting may be the reason for refusal of hormonal replacement therapy .

Use of tacrolimus in rescue therapy of acute and chronic rejection in liver transplantation

PURPOSE: To study the indications and results of tacrolimus as rescue therapy for acute cellular or chronic rejection in liver transplantation. PATIENTS AND METHODS: Eighteen liver transplant recipients who underwent rescue therapy with tacrolimus between March 1995 and August 1999 were retrospectively studied. The treatment indication, patients, and graft situation were recorded as of October 31st, 1999. The response to tacrolimus was defined as patient survival with a functional graft and histological reversal of acute cellular, or for chronic rejection, bilirubin serum levels decreasing to up to twice the upper normal limit. RESULTS: Fourteen cases (77.8%) presented a good response. The response rate for the different indications was: (1) acute cellular + sepsis - 0/1 case; (2) recurrent acute cellular - 1/1 case; (3) OKT3-resistant acute cellular - 2/2 cases; (4) steroid-resistant acute cellular + active viral infection - 3/3 cases; (5) chronic rejection - 8/11 cases (72.7% response rate). The 4 patients who did not respond died. CONCLUSION: Tacrolimus rescue therapy was successful in most cases of acute cellular and chronic rejection in liver transplantation.

Ecstasy intoxication: the toxicological basis for treatment

Youngsters are increasingly using 3,4 methylenedioxymethamphetamine, known as ecstasy, because it is wrongly believed that it does not induce harm. However, there are many reports of adverse effects, including acute intoxication, abuse potential, and possible neurotoxic effects. Therefore, health care providers need to promptly recognize the symptoms of systemic intoxication in order to initiate early treatment. The drug is used by the oral route for long hours during crowded dance parties. Acutely, ecstasy increases the release of serotonin and decreases its reuptake, leading to hypertension, hyperthermia, trismus, and vomiting. There is debate on whether recreational doses of ecstasy cause permanent damage to human serotonergic neurons. Ecstasy users showed a high risk of developing psychopathological disturbances. The prolonged use of ecstasy might induce dependence, characterized by tolerance and hangover. Acute ecstasy intoxication needs emergency-type treatment to avoid the dose-dependent increase in adverse reactions and in severity of complications. There are no specific antidotes to be used during acute intoxication. Supportive measures and medical treatment for each one of the complications should be implemented, keeping in mind that symptoms originate mainly from the central nervous system and the cardiovascular system.

The effect of intravenous zoledronic acid on glucocorticoid-induced multiple vertebral fractures in juvenile systemic lupus erythematosus

Glucocorticoids are widely used in the treatment of lupus patients, and adverse effects, which include osteoporosis and associated fractures, are frequent. Treatment of osteoporosis of young patients should be effective and not harmful to bone growth and remodeling. Bisphosphonates are drugs that decrease the incidence of bone fractures, but their use in juvenile patients is still controversial because of their possible side effects on the growing skeleton. However, recently published studies showed that linear growth continued normally after treatment with these drugs, and there was no excessive suppression of bone remodeling or mineralization defects. Zoledronic acid is a new intravenous bisphosphonate that has been approved by the US FDA for use with hypercalcemia of malignancies and might be an effective treatment for postmenopausal osteoporosis. The authors report a case of a young girl with systemic lupus who developed multiple vertebral collapses due to glucocorticoid therapy, and zoledronic acid was used producing significant clinical and densitometric improvement.

Effects of medical therapy, alcohol, smoking, and endocrine disruptors on male infertility

Infertility affects up to 15% of the sexually active population, and in 50% of cases, a male factor is involved, either as a primary problem or in combination with a problem in the female partner. Because many commonly encountered drugs and medications can have a detrimental effect on male fertility, the medical evaluation should include a discussion regarding the use of recreational and illicit drugs, medications, and other substances that may impair fertility. With the knowledge of which drugs and medications may be detrimental to fertility, it may be possible to modify medication regimens or convince a patient to modify habits to decrease adverse effects on fertility and improve the chances of achieving a successful pregnancy. Concern is growing that male sexual development and reproduction have changed for the worse over the past 30 to 50 years. Although some reports find no changes, others suggest that sperm counts appear to be decreasing and that the incidence of developmental abnormalities such as hypospadias and cryptorchidism appears to be increasing, as is the incidence of testicular cancer. These concerns center around the possibility that our environment is contaminated with chemicals - both natural and synthetic - that can interact with the endocrine system.

Antidepressant induced excessive yawning and indifference

Introduction Antidepressant induced excessive yawning has been described as a possible side effect of pharmacotherapy. A syndrome of indifference has also been described as another possible side effect. The frequency of those phenomena and their physiopathology are unknown. They are both considered benign and reversible after antidepressant discontinuation but severe cases with complications as temporomandibular lesions, have been described. Methods We report two unprecedented cases in which excessive yawning and indifference occurred simultaneously as side effects of antidepressant therapy, discussing possible physiopathological mechanisms for this co-occurrence. Case 1: A male patient presented excessive yawning (approximately 80/day) and apathy after venlafaxine XR treatment. Symptoms reduced after a switch to escitalopram, with a reduction to 50 yawns/day. Case 2: A female patient presented excessive yawning (approximately 25/day) and inability to react to environmental stressors with desvenlafaxine. Conclusion Induction of indifference and excessive yawning may be modulated by serotonergic and noradrenergic mechanisms. One proposal to unify these side effects would be enhancement of serotonin in midbrain, especially paraventricular and raphe nucleus.

Brazilian multicenter study on efficacy and tolerability of trandolapril in mild-to-moderate essential arterial hypertension. EMBATHE substudy with ambulatory blood pressure monitoring

OBJECTIVE: A double-blind, placebo-controlled multicenter study involving 34 centers from different Brazilian regions was performed to evaluate the antihypertensive efficacy and tolerability of trandolapril, an angiotensin I converting enzyme inhibitor, in the treatment of mild-to-moderate systemic arterial hypertension. METHODS: Of 262 patients enrolled in this study, 127 were treated with trandolapril 2 mg/day for 8 consecutive weeks, and the remaining 135 patients received placebo for the same period of time. Reduction in blood pressure (BP) and the occurrence of adverse events during this period were evaluated in both groups. RESULTS: Significant reductions in both systolic and diastolic pressures were observed in patients treated with trandolapril when compared with those on placebo. Antihypertensive efficacy was achieved in 57.5% of the patients on trandolapril and in 42% of these normal values of BP were obtained. The efficacy of trandolapril was similar in all centers, regardless of the area of the country. In a subset of 30 patients who underwent ABPM, responders showed a significant hypotensive effect to trandolapril throughout the 24 hour day. The adverse event profile was similar in both trandolapril and placebo groups. CONCLUSION: Our results demonstrate, for the first time in a large group of hypertensive patients from different regions in Brazil, good efficacy and tolerability of trandolapril during treatment of mild-to-moderate essential systemic hypertension.

Safety and efficacy of coronary stent implantation. Acute and six month outcomes of 1,126 consecutive patients treated in 1996 and 1997

PURPOSE: The authors analyzed the 30-day and 6-month outcomes of 1,126 consecutive patients who underwent coronary stent implantation in 1996 and 1997. METHODS: The 30-day results and 6-month angiographic follow-up were analyzed in patients treated with coronary stents in 1996 and 1997. All patients underwent coronary stenting with high-pressure implantation (>12 atm) and antiplatelet drug regimen (aspirin plus ticlopidine). RESULTS: During the study period, 1,390 coronary stents were implanted in 1,200 vessels of 1,126 patients; 477 patients were treated in the year 1996 and 649 in 1997. The number of percutaneous procedures performed using stents increased significantly in 1997 compared to 1996 (64 % vs 48%, p=0.0001). The 30-day results were similar in both years; the success and stent thrombosis rates were equal (97% and 0.8%, respectively). The occurrence of new Q wave MI (1.3% vs 1.1%, 1996 vs 1997, p=NS), emergency coronary bypass surgery (1% vs 0.6%, 1996 vs 1997, p=NS) and 30-day death rates (0.2% vs 0.5%, 1996 vs 1997, p=NS) were similar. The 6-month restenosis rate was 25% in 1996 and 27% in 1997 (p= NS); the target vessel revascularization rate was 15% in 1996 and 16% in 1997 (p = NS). CONCLUSIONS: Intracoronary stenting showed a high success rate and a low incidence of 30-day occurrence of new major coronary events in both periods, despite the greater angiographic complexity of the patients treated with in 1997. These adverse variables did not have a negative influence at the 6-month clinical and angiographic follow-up, with similar rates of restenosis and ischemia-driven target lesion revascularization rates.

Primary coronary angioplasty and stent implantation in acute myocardial infarction. Comparative analysis of the in-hospital results in the CENIC/SBHCI registry

OBJECTIVE: Comparative analysis of the in-hospital results after primary implantation of stents or coronary balloon angioplasty in patients with acute myocardial infarction (MI). METHODS: CENIC (National Center of Cardiovascular Interventions) gathered data on 3,924 patients undergoing coronary angioplasty (in the primary form, without the previous use of thrombolytic agents) in the first 24 hours after a MI, during the period of 1996-1998. From these 3,924 patients, 1,337 (34%) underwent stent implantation. We analyzed the success of the procedure and the occurrence of adverse cardiac events. RESULTS: In patients undergoing stent implantation there were more males (77% vs 69%, p=0.001), previous by pass surgery (6.3% vs. 4.5%, p=0.01), anterior MI and stent implantation in left descending artery (55% vs. 48% vs. p=0.009), and saphenous vein bypass grafts (3.3% vs. 1.9%). the procedure was more succesful in the group of stents (97% vs. 84%, p=0.001) and reinfarction rate (2.5 vs. 4%, p=0.002). The need for emergency revascularization was similar (1% vs. 1.1%, NS). Total in-hospital mortality was lower in stent group (3.4% vs. 7. 2%, p=0.0001) and this effect was in patients Killip class III/V (19.5% vs. 32.5%, p= 0.002) because there was no difference in patients class I/II (1.7% vs. 2.8%, p=0.9). CONCLUSION: Primary stent implantation in acute myocardial infarction showed better early results than balloon angioplasty alome.

Beta-adrenergic blocking agents in heart failure

Cardiac dysfunction in heart failure is widely recognized as a progressive process, regardless of the clinical signs and symptoms. An increase in cardiac sympathetic drive is one of the earliest neurohormonal responses occurring in patients with heart failure and may be one of the major causes of the progressive remodeling leading to the decline in myocardial function, and responsible for the poor prognosis of patients with heart failure. Therefore, recent data provided by several appropriately designed clinical trials clearly indicate the benefits of beta-adrenoceptor blocking agents, combined with diuretics, ACE inhibitors, and digoxin in chronic heart failure class II to IV due to systolic ventricular dysfunction. The benefits are related to symptoms, functional capacity, remodeling, and improvement in left ventricular function, reduction in cardiovascular hospitalization, a decrease in the overall and sudden cardiac death rate, and are similar in patients with ischemic or nonischemic cardiomyopathy, independent of age, gender, or functional class. In this review we describe the cardiovascular effects of the increase in sympathetic drive, the pharmacological properties of the beta-blockers most evaluated in heart failure therapy (metoprolol, bisoprolol, and carvedilol), the major clinical trials related to these agents in heart failure, the recommendations for their appropriate use in clinical practice, the precautions to be adopted, and how to handle the more common adverse reactions.

Clinical significance of in-hospital reocclusion after mechanical reperfusion and percutaneous transluminal coronary angioplasty for acute myocardial infarction

OBJECTIVE: To analyze the effects of in-hospital reocclusion of reperfused AMI culprit coronary arteries in mortality and to identify the predictors. METHODS: The present study comprises a sample of 155 patients with AMI who underwent successful mechanical reperfusion by direct coronary angioplasty and angiographic control during hospitalization or before discharge. Patients were classified into group A: reoccluded patients (n=30) and group B: non-reoccluded patients (n=125). RESULTS: We identified in-hospital reocclusion predictors and found a greater significance in mortality among reoccluded patients (23,3% x 1.6%; p=0.00004). Silent reocclusion or typical angina at reocclusion had a good prognosis. The independent predictors of in-hospital mortality were hypertension, multiarterial lesions, totally occluded AMI culprit lesions, failed redilatation, failed redilatation in comparison with no intention to redilate, no redilatation in comparison with no atempt to redilate, and reocclusion within the first 48 to 72 hours. The decision to redilate, independently of the result, led to a 50.0% reduction in hospital mortality (p=0.0366). CONCLUSION: In-hospital AMI culprit coronary artery reocclusion had an adverse effect similar to that reported in clinical studies with high mortality rates (23.3% x 1.6%; p=0.00004). The major contribution of this study is to recommend the reopening of reoccluded AMI culprit coronary arteries as a means for the management of coronary artery reocclusion.

Acute myocardial infarction in progressively elderly patients. A comparative analysis of immediate results in patients who underwent primary percutaneous coronary intervention

OBJECTIVE: Analysis of the in-hospital results, in progressively elderly patients who undergo primary percutaneous coronary intervention (PCI) in the first 24 hours of AMI. METHODS: The patients were divided into three different age groups (60/69, 70/79, and > or = 80 years) and were treated from 7/95 until 12/99. The primary success rate and the occurrence of major clinical events were analyzed at the end of the in-hospital phase. Coronary stent implantation and abciximab use were employed at the intervencionist discretion. RESULTS: We analyzed 201 patients with age ranging from 60 to 93 years, who underwent primary PCI. Patients with ages above 70 were more often female (p=.015). Those with ages above 80 were treated later with PCI (p=.054), and all of them presented with total occlusion of the infarct-related artery. Coronary stents were implanted in 30% of the patients. Procedural success was lower in > or = 80 year old patients (p=.022), and the death rate was higher in > or = 70 years olds (p=.019). Reinfarction and coronary bypass surgery were uncommon events. A trend occurred toward a higher combined incidence of major in-hospital events according to increased age (p=.064). CONCLUSION: Elderly patients ( > or = 70 years) presented with adverse clinical and angiographic profiles and patients > or = 80 years of age obtained reduced TIMI 3 flow success rates after primary PTCA, and those > or = 70 years had a higher death rate.

One-year follow-up after primary coronary intervention for acute myocardial infarction in diabetic patients: a substudy of the STENT PAMI trial

OBJECTIVE - This analysis was undertaken to determine the composite incidence of cumulative adverse events (death, reinfarction, disabling stroke, and target vessel revascularization) at the end of the first year after acute myocardial infarction, in diabetic patients who underwent coronary stenting or primary coronary balloon angioplasty. METHODS - From the STENT PAMI trial, we analyzed the 6-month angiographic and 1-year clinical outcomes of 135 diabetic (112, noninsulin dependent) patients who underwent the randomization process of the trial and compared them with 758 nondiabetic patients. RESULTS - Coronary stenting did not significantly reduce the primary composite clinical end point when compared with PTCA (20 vs. 30%, p=0.2). A significant benefit from stenting was observed in patients with noninsulin dependent diabetes, with a trend toward a lesser need for new revascularization procedures (10 vs. 21%, p<.001), with a significant reduction in the primary composite clinical end point at 1 year (12 vs. 28%, p=. 04). At 6 months, the restenosis rate were significantly reduced only in nondiabetic patients (18 vs. 33%, p<. 001). Diabetic patients had the same restenosis rate (38%) either with stenting or balloon PTCA. CONCLUSIONS - Coronary Stenting in diabetics noninsulin dependent offered a significant reduction in the composite incidence of major clinical adverse events compared with balloon PTCA.